Alfred Bothwell, PhD
Professor Emeritus of Immunobiology; Member of HTI and VBT
Research & Publications
Biography
News
Research Summary
To characterize the development and function of regulatory T cells and characterize mechanisms that affect cancer, autoimmunity, inflammation, transplantation and recruitment into vascular sites.
Extensive Research Description
The
research goals of the lab are to characterize the development and function of
regulatory T cells and characterize mechanisms that affect autoimmunity,
inflammation, transplantation and recruitment into vascular sites. Both mouse and human responses are
studied in vitro and in vivo which includes the development and use of
humanized mice. In addition, our
experience with synthetic microvessels has lead to a translational project to
revascularize islets to treat type I diabetes.
Specific accomplishments in the last year:
Specific accomplishments in the last year:
- PPARs: Peroxysome proliferated activated receptors (PPARs) represent a group of transcription factors that are critical in regulating glucose and lipid metabolism. Ligands of PPARg inhibit metabolically induced arteriosclerosis and also prevent the development of inflammatory disorders in several experimental mouse models including EAE, asthma, rheumatic arthritis and sepsis. The role of PPARg in graft arteriosclerosis (GA) has not been characterized. We therefore tested the in vivo effects of administration of the endogenously occurring ligand, 15 deoxy-prostaglandin-J2 (15-d-PGJ2), and ciglitazone and pioglitazone on vascular remodeling of human artery induced by alloreactive PBMC and the IFN-g model. The data indicate that 15-d-PGJ2 and pioglitazone significantly inhibit human GA in our in vivo human arterial graft model in immunodeficient mice. These effects appear specific because they are reversed by treatment with an antagonist, GW9662. Preliminary results suggest that it is possible to reverse disease once it is established for 3 weeks in this model.
- Microorgan Islet Grafts: The goal of this project is to bioengineer pancreatic beta cell-containing implants for treatment of diabetes. Casting the islets together with EC in collagen gels effectively revascularizes the islets in SCID/bg mice. Indeed, our pilot data indicate that these human islet-EC microorgans secrete human insulin into the peripheral blood of mice for periods of at least 4 months and demonstrate responsiveness to glucose in glucose tolerance tests. We are characterizing the structure/function properties of these microorgans in detail, including the microvessel structure and the stability of the microvessels with time. During the last year we (with Serge Kobsa and M. Saltzman) are characterizing new nanospheres that have a greater capacity to secrete factors for longer periods of time. We have shown that Hepatocyte Growth Factor (HGF) has significant anti-apoptotic activity on islets in vitro and hope to evaluate this with the new delivery systems in vivo. Inflammation and Colon Cancer: The APC/Min mouse is a highly studied model of intestinal tumorigenesis. During the last year we have shown that APC/Min mice that are deficient in the proinflammatory cytokine IL-17A have a 90% reduction in small intestinal polyps. We hope to define both the source of the IL-17A that is critical as well as the cell type that is the target of this cytokine.
Coauthors
Research Interests
Biochemistry; Biology; Biomedical Engineering; Immunogenetics
Selected Publications
- Functional Diversity of Myeloid-Derived Suppressor Cells: The Multitasking Hydra of Cancer.Jayakumar A, Bothwell ALM. Functional Diversity of Myeloid-Derived Suppressor Cells: The Multitasking Hydra of Cancer. The Journal Of Immunology 2019, 203: 1095-1103. PMID: 31427398, PMCID: PMC6703177, DOI: 10.4049/jimmunol.1900500.
- Dickkopf1: An immunomodulatory ligand and Wnt antagonist in pathological inflammationChae WJ, Bothwell ALM. Dickkopf1: An immunomodulatory ligand and Wnt antagonist in pathological inflammation. Differentiation 2019, 108: 33-39. PMID: 31221431, PMCID: PMC6982462, DOI: 10.1016/j.diff.2019.05.003.
- Ripk3-induced inflammation by I-MDSCs promotes intestinal tumorsJayakumar A, Bothwell ALM. Ripk3-induced inflammation by I-MDSCs promotes intestinal tumors. Cancer Research 2019, 79: canres.2153.2018. PMID: 30786994, PMCID: PMC7395226, DOI: 10.1158/0008-5472.can-18-2153.
- Canonical and Non-Canonical Wnt Signaling in Immune CellsChae WJ, Bothwell ALM. Canonical and Non-Canonical Wnt Signaling in Immune Cells. Trends In Immunology 2018, 39: 830-847. PMID: 30213499, PMCID: PMC7367500, DOI: 10.1016/j.it.2018.08.006.
- Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejectionLim S, Kirkiles-Smith NC, Pober JS, Bothwell ALM, Choi JM. Regulation of human T cell responses by dNP2-ctCTLA-4 inhibits human skin and microvessel graft rejection. Biomaterials 2018, 183: 128-138. PMID: 30165256, PMCID: PMC6141312, DOI: 10.1016/j.biomaterials.2018.08.049.
- Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone miceMoon JS, Mun CH, Kim JH, Cho JY, Park SD, Park TY, Shin JS, Ho CC, Park YB, Ghosh S, Bothwell ALM, Lee SW, Lee SK. Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice. Kidney International 2018, 93: 1118-1130. PMID: 29409726, DOI: 10.1016/j.kint.2017.11.017.
- Therapeutic Potential of Gene-Modified Regulatory T Cells: From Bench to BedsideChae WJ, Bothwell ALM. Therapeutic Potential of Gene-Modified Regulatory T Cells: From Bench to Bedside. Frontiers In Immunology 2018, 9: 303. PMID: 29503652, PMCID: PMC5820299, DOI: 10.3389/fimmu.2018.00303.
- DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activationXiao Q, Wu J, Wang WJ, Chen S, Zheng Y, Yu X, Meeth K, Sahraei M, Bothwell ALM, Chen L, Bosenberg M, Chen J, Sexl V, Sun L, Li L, Tang W, Wu D. DKK2 imparts tumor immunity evasion through β-catenin-independent suppression of cytotoxic immune-cell activation. Nature Medicine 2018, 24: 262-270. PMID: 29431745, PMCID: PMC5840007, DOI: 10.1038/nm.4496.
- Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitisChae W, Park J, Henegariu O, Yilmaz S, Hao L, Bothwell ALM. Membrane‐bound Dickkopf‐1 in Foxp3+ regulatory T cells suppresses T‐cell‐mediated autoimmune colitis. Immunology 2017, 152: 265-275. PMID: 28556921, PMCID: PMC5588763, DOI: 10.1111/imm.12766.
- Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 ResponseJayakumar A, Bothwell ALM. Stat6 Promotes Intestinal Tumorigenesis in a Mouse Model of Adenomatous Polyposis by Expansion of MDSCs and Inhibition of Cytotoxic CD8 Response. Neoplasia 2017, 19: 595-605. PMID: 28654863, PMCID: PMC5487300, DOI: 10.1016/j.neo.2017.04.006.
- Snapshots of CD4 + T cell plasticity in the pathogenesis of allergic asthmaChae WJ, Bothwell AL. Snapshots of CD4 + T cell plasticity in the pathogenesis of allergic asthma. Journal Of Thoracic Disease 2016, 8: e1010-e1012. PMID: 27747048, PMCID: PMC5059289, DOI: 10.21037/jtd.2016.08.19.
- Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 DifferentiationPark HJ, Park HS, Lee JU, Bothwell AL, Choi JM. Sex-Based Selectivity of PPARγ Regulation in Th1, Th2, and Th17 Differentiation. International Journal Of Molecular Sciences 2016, 17: 1347. PMID: 27548145, PMCID: PMC5000743, DOI: 10.3390/ijms17081347.
- Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogenPark HJ, Park HS, Lee JU, Bothwell AL, Choi JM. Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen. Scientific Reports 2016, 6: 28495. PMID: 27335315, PMCID: PMC4917844, DOI: 10.1038/srep28495.
- The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated InflammationChae WJ, Ehrlich AK, Chan PY, Teixeira AM, Henegariu O, Hao L, Shin JH, Park JH, Tang WH, Kim ST, Maher SE, Goldsmith-Pestana K, Shan P, Hwa J, Lee PJ, Krause DS, Rothlin CV, McMahon-Pratt D, Bothwell AL. The Wnt Antagonist Dickkopf-1 Promotes Pathological Type 2 Cell-Mediated Inflammation. Immunity 2016, 44: 246-258. PMID: 26872695, PMCID: PMC4758884, DOI: 10.1016/j.immuni.2016.01.008.
- Blocking MHC class II on human endothelium mitigates acute rejectionAbrahimi P, Qin L, Chang WG, Bothwell AL, Tellides G, Saltzman WM, Pober JS. Blocking MHC class II on human endothelium mitigates acute rejection. JCI Insight 2016, 1: e85293. PMID: 26900601, PMCID: PMC4756651, DOI: 10.1172/jci.insight.85293.
- dNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitisLim S, Kim WJ, Kim YH, Lee S, Koo JH, Lee JA, Yoon H, Kim DH, Park HJ, Kim HM, Lee HG, Yun Kim J, Lee JU, Hun Shin J, Kyun Kim L, Doh J, Kim H, Lee SK, Bothwell AL, Suh M, Choi JM. dNP2 is a blood–brain barrier-permeable peptide enabling ctCTLA-4 protein delivery to ameliorate experimental autoimmune encephalomyelitis. Nature Communications 2015, 6: 8244. PMID: 26372309, PMCID: PMC4579786, DOI: 10.1038/ncomms9244.
- Spontaneous Intestinal Tumorigenesis in Apc/Min+ Mice Requires Altered T Cell Development with IL-17AChae WJ, Bothwell AL. Spontaneous Intestinal Tumorigenesis in Apc/Min+ Mice Requires Altered T Cell Development with IL-17A. Journal Of Immunology Research 2015, 2015: 860106. PMID: 26146642, PMCID: PMC4469837, DOI: 10.1155/2015/860106.
- The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis InfectionEhrlich A, Castilho TM, Goldsmith-Pestana K, Chae WJ, Bothwell AL, Sparwasser T, McMahon-Pratt D. The Immunotherapeutic Role of Regulatory T Cells in Leishmania (Viannia) panamensis Infection. The Journal Of Immunology 2014, 193: 2961-2970. PMID: 25098291, PMCID: PMC4170189, DOI: 10.4049/jimmunol.1400728.
- Intranuclear interactomic inhibition of FoxP3 suppresses functions of Treg cells.Park JH, Ko JS, Shin Y, Cho JY, Oh HA, Bothwell AL, Lee SK. Intranuclear interactomic inhibition of FoxP3 suppresses functions of Treg cells. Biochemical And Biophysical Research Communications 2014, 451: 1-7. PMID: 25044110, DOI: 10.1016/j.bbrc.2014.06.141.
- PPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center FormationPark HJ, Kim DH, Choi JY, Kim WJ, Kim JY, Senejani AG, Hwang SS, Kim LK, Tobiasova Z, Lee GR, Craft J, Bothwell AL, Choi JM. PPARγ Negatively Regulates T Cell Activation to Prevent Follicular Helper T Cells and Germinal Center Formation. PLOS ONE 2014, 9: e99127. PMID: 24921943, PMCID: PMC4055678, DOI: 10.1371/journal.pone.0099127.
- A Humanized Mouse Model of Autoimmune InsulitisMilam A, Maher SE, Gibson JA, Lebastchi J, Wen L, Ruddle NH, Herold KC, Bothwell AL. A Humanized Mouse Model of Autoimmune Insulitis. Diabetes 2014, 63: 1712-1724. PMID: 24478396, PMCID: PMC3994947, DOI: 10.2337/db13-1141.
- Interplay between DNA repair and inflammation, and the link to cancerKidane D, Chae WJ, Czochor J, Eckert KA, Glazer PM, Bothwell AL, Sweasy JB. Interplay between DNA repair and inflammation, and the link to cancer. Critical Reviews In Biochemistry And Molecular Biology 2014, 49: 116-139. PMID: 24410153, PMCID: PMC4300235, DOI: 10.3109/10409238.2013.875514.
- Mutation of POLB Causes Lupus in MiceSenejani AG, Liu Y, Kidane D, Maher SE, Zeiss CJ, Park HJ, Kashgarian M, McNiff JM, Zelterman D, Bothwell AL, Sweasy JB. Mutation of POLB Causes Lupus in Mice. Cell Reports 2014, 6: 1-8. PMID: 24388753, PMCID: PMC3916967, DOI: 10.1016/j.celrep.2013.12.017.
- Neuroprotection against neuroblastoma cell death induced by depletion of mitochondrial glutathioneDukhande VV, Kawikova I, Bothwell AL, Lai JC. Neuroprotection against neuroblastoma cell death induced by depletion of mitochondrial glutathione. Apoptosis 2013, 18: 702-712. PMID: 23494481, PMCID: PMC3645366, DOI: 10.1007/s10495-013-0836-4.
- An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness woundsKobsa S, Kristofik NJ, Sawyer AJ, Bothwell AL, Kyriakides TR, Saltzman WM. An electrospun scaffold integrating nucleic acid delivery for treatment of full-thickness wounds. Biomaterials 2013, 34: 3891-3901. PMID: 23453058, PMCID: PMC3625647, DOI: 10.1016/j.biomaterials.2013.02.016.
- The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune DiseasesChoi JM, Bothwell AL. The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases. Molecules And Cells 2012, 33: 217-222. PMID: 22382683, PMCID: PMC3887706, DOI: 10.1007/s10059-012-2297-y.
- Risperidone-Related Improvement of Irritability in Children with Autism Is not Associated with Changes in Serum of Epidermal Growth Factor and Interleukin-13Tobiasova Z, van der Lingen KH, Scahill L, Leckman JF, Zhang Y, Chae W, McCracken JT, McDougle CJ, Vitiello B, Tierney E, Aman MG, Arnold LE, Katsovich L, Hoekstra PJ, Volkmar F, Bothwell AL, Kawikova I. Risperidone-Related Improvement of Irritability in Children with Autism Is not Associated with Changes in Serum of Epidermal Growth Factor and Interleukin-13. Journal Of Child And Adolescent Psychopharmacology 2011, 21: 555-564. PMID: 22070180, PMCID: PMC3279715, DOI: 10.1089/cap.2010.0134.
- Reperfusion Injury Intensifies the Adaptive Human T Cell Alloresponse in a Human-Mouse Chimeric Artery ModelYi T, Fogal B, Hao Z, Tobiasova Z, Wang C, Rao DA, Al-Lamki RS, Kirkiles-Smith NC, Kulkarni S, Bradley JR, Bothwell AL, Sessa WC, Tellides G, Pober JS. Reperfusion Injury Intensifies the Adaptive Human T Cell Alloresponse in a Human-Mouse Chimeric Artery Model. Arteriosclerosis Thrombosis And Vascular Biology 2011, 32: 353-360. PMID: 22053072, PMCID: PMC3262100, DOI: 10.1161/atvbaha.111.239285.
- IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ miceChae WJ, Bothwell AL. IL-17F deficiency inhibits small intestinal tumorigenesis in ApcMin/+ mice. Biochemical And Biophysical Research Communications 2011, 414: 31-36. PMID: 21939640, DOI: 10.1016/j.bbrc.2011.09.016.
- Peroxisome Proliferator–Activated Receptor-γ Agonists Prevent In Vivo Remodeling of Human Artery Induced by Alloreactive T CellsTobiasova Z, Zhang L, Yi T, Qin L, Manes TD, Kulkarni S, Lorber MI, Rodriguez FC, Choi JM, Tellides G, Pober JS, Kawikova I, Bothwell AL. Peroxisome Proliferator–Activated Receptor-γ Agonists Prevent In Vivo Remodeling of Human Artery Induced by Alloreactive T Cells. Circulation 2011, 124: 196-205. PMID: 21690493, PMCID: PMC3347886, DOI: 10.1161/circulationaha.110.015396.
- Altered immunoglobulin profiles in children with Tourette syndromeBos-Veneman NG, Olieman R, Tobiasova Z, Hoekstra PJ, Katsovich L, Bothwell AL, Leckman JF, Kawikova I. Altered immunoglobulin profiles in children with Tourette syndrome. Brain Behavior And Immunity 2010, 25: 532-538. PMID: 21156204, PMCID: PMC3056238, DOI: 10.1016/j.bbi.2010.12.003.
- Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammationChoi JM, Shin JH, Sohn MH, Harding MJ, Park JH, Tobiasova Z, Kim DY, Maher SE, Chae WJ, Park SH, Lee CG, Lee SK, Bothwell AL. Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 18575-18580. PMID: 20937878, PMCID: PMC2972952, DOI: 10.1073/pnas.1000400107.
- An Implantable Vascularized Protein Gel Construct That Supports Human Fetal Hepatoblast Survival and Infection by Hepatitis C Virus in MiceHarding MJ, Lepus CM, Gibson TF, Shepherd BR, Gerber SA, Graham M, Paturzo FX, Rahner C, Madri JA, Bothwell AL, Lindenbach BD, Pober JS. An Implantable Vascularized Protein Gel Construct That Supports Human Fetal Hepatoblast Survival and Infection by Hepatitis C Virus in Mice. PLOS ONE 2010, 5: e9987. PMID: 20376322, PMCID: PMC2848675, DOI: 10.1371/journal.pone.0009987.
- Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesisChae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL. Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 5540-5544. PMID: 20212110, PMCID: PMC2851824, DOI: 10.1073/pnas.0912675107.
- Elevated expression of MCP-1, IL-2 and PTPR-N in basal ganglia of Tourette syndrome casesMorer A, Chae W, Henegariu O, Bothwell AL, Leckman JF, Kawikova I. Elevated expression of MCP-1, IL-2 and PTPR-N in basal ganglia of Tourette syndrome cases. Brain Behavior And Immunity 2010, 24: 1069-1073. PMID: 20193755, DOI: 10.1016/j.bbi.2010.02.007.
- Children with Tourette's Syndrome May Suffer Immunoglobulin A Dysgammaglobulinemia: Preliminary ReportKawikova I, Grady BP, Tobiasova Z, Zhang Y, Vojdani A, Katsovich L, Richmand BJ, Park TW, Bothwell AL, Leckman JF. Children with Tourette's Syndrome May Suffer Immunoglobulin A Dysgammaglobulinemia: Preliminary Report. Biological Psychiatry 2009, 67: 679-683. PMID: 20006327, PMCID: PMC3974615, DOI: 10.1016/j.biopsych.2009.09.034.
- Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiationDas J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, Van Kaer L, Shi Y, Das G. Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation. Journal Of Experimental Medicine 2009, 206: 2407-2416. PMID: 19808254, PMCID: PMC2768861, DOI: 10.1084/jem.20082286.
- Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/γc−/−, Balb/c-Rag1−/−γc−/−, and C.B-17-scid/bg immunodeficient miceLepus CM, Gibson TF, Gerber SA, Kawikova I, Szczepanik M, Hossain J, Ablamunits V, Kirkiles-Smith N, Herold KC, Donis RO, Bothwell AL, Pober JS, Harding MJ. Comparison of human fetal liver, umbilical cord blood, and adult blood hematopoietic stem cell engraftment in NOD-scid/γc−/−, Balb/c-Rag1−/−γc−/−, and C.B-17-scid/bg immunodeficient mice. Human Immunology 2009, 70: 790-802. PMID: 19524633, PMCID: PMC2949440, DOI: 10.1016/j.humimm.2009.06.005.
- Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritisChoi JM, Kim SH, Shin JH, Gibson T, Yoon BS, Lee DH, Lee SK, Bothwell AL, Lim JS, Lee SK. Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 19875-19880. PMID: 19066215, PMCID: PMC2604944, DOI: 10.1073/pnas.0805198105.
- Promotion of β-Cell Differentiation in Pancreatic Precursor Cells by Adult Islet CellsChen W, Begum S, Opare-Addo L, Garyu J, Gibson TF, Bothwell AL, Papaioannou VE, Herold KC. Promotion of β-Cell Differentiation in Pancreatic Precursor Cells by Adult Islet Cells. Endocrinology 2008, 150: 570-579. PMID: 18845629, PMCID: PMC2646532, DOI: 10.1210/en.2008-1009.
- Pax5 and Linker Histone H1 Coordinate DNA Methylation and Histone Modifications in the 3′ Regulatory Region of the Immunoglobulin Heavy Chain LocusGiambra V, Volpi S, Emelyanov AV, Pflugh D, Bothwell AL, Norio P, Fan Y, Ju Z, Skoultchi AI, Hardy RR, Frezza D, Birshtein BK. Pax5 and Linker Histone H1 Coordinate DNA Methylation and Histone Modifications in the 3′ Regulatory Region of the Immunoglobulin Heavy Chain Locus. Molecular And Cellular Biology 2008, 28: 6123-6133. PMID: 18644860, PMCID: PMC2547000, DOI: 10.1128/mcb.00233-08.
- Amelioration of Human Allograft Arterial Injury by Atorvastatin or Simvastatin Correlates With Reduction of Interferon-γ Production by Infiltrating T CellsYi T, Rao DA, Tang PC, Wang Y, Cuchara LA, Bothwell AL, Colangelo CM, Tellides G, Pober JS, Lorber MI. Amelioration of Human Allograft Arterial Injury by Atorvastatin or Simvastatin Correlates With Reduction of Interferon-γ Production by Infiltrating T Cells. Transplantation 2008, 86: 719-727. PMID: 18791454, PMCID: PMC2650813, DOI: 10.1097/tp.0b013e318183eefa.
- Interferon-γ Induces X-linked Inhibitor of Apoptosis-associated Factor-1 and Noxa Expression and Potentiates Human Vascular Smooth Muscle Cell Apoptosis by STAT3 Activation*Bai Y, Ahmad U, Wang Y, Li JH, Choy JC, Kim RW, Kirkiles-Smith N, Maher SE, Karras JG, Bennett CF, Bothwell AL, Pober JS, Tellides G. Interferon-γ Induces X-linked Inhibitor of Apoptosis-associated Factor-1 and Noxa Expression and Potentiates Human Vascular Smooth Muscle Cell Apoptosis by STAT3 Activation*. Journal Of Biological Chemistry 2008, 283: 6832-6842. PMID: 18192275, DOI: 10.1074/jbc.m706021200.
- Regulatory Transplantation Tolerance and “Stemness”: Evidence That Foxp3 May Play a Regulatory Role in SOCS-3 Gene TranscriptionMuthukumarana P, Chae WJ, Maher S, Rosengard BR, Bothwell AL, Metcalfe SM. Regulatory Transplantation Tolerance and “Stemness”: Evidence That Foxp3 May Play a Regulatory Role in SOCS-3 Gene Transcription. Transplantation 2007, 84: s6-s11. PMID: 17632414, DOI: 10.1097/01.tp.0000269116.06510.db.
- Natural killer T cells and CD8+ T cells are dispensable for T cell–dependent allergic airway inflammationDas J, Eynott P, Jupp R, Bothwell A, Van Kaer L, Shi Y, Das G. Natural killer T cells and CD8+ T cells are dispensable for T cell–dependent allergic airway inflammation. Nature Medicine 2006, 12: 1345-1346. PMID: 17151684, DOI: 10.1038/nm1206-1345.
- Pivotal roles of CD8+ T cells restricted by MHC class I–like molecules in autoimmune diseasesDas G, Das J, Eynott P, Zhang Y, Bothwell AL, Van Kaer L, Shi Y. Pivotal roles of CD8+ T cells restricted by MHC class I–like molecules in autoimmune diseases. Journal Of Experimental Medicine 2006, 203: 2603-2611. PMID: 17088432, PMCID: PMC2118151, DOI: 10.1084/jem.20060936.
- Manganese Treatment Modulates the Expression of Peroxisome Proliferator-activated Receptors in Astrocytoma and Neuroblastoma CellsIsaac AO, Kawikova I, Bothwell AL, Daniels CK, Lai JC. Manganese Treatment Modulates the Expression of Peroxisome Proliferator-activated Receptors in Astrocytoma and Neuroblastoma Cells. Neurochemical Research 2006, 31: 1305-1316. PMID: 17053972, DOI: 10.1007/s11064-006-9173-0.
- Decreased Numbers of Regulatory T Cells Suggest Impaired Immune Tolerance in Children with Tourette Syndrome: A Preliminary StudyKawikova I, Leckman JF, Kronig H, Katsovich L, Bessen DE, Ghebremichael M, Bothwell AL. Decreased Numbers of Regulatory T Cells Suggest Impaired Immune Tolerance in Children with Tourette Syndrome: A Preliminary Study. Biological Psychiatry 2006, 61: 273-278. PMID: 16996487, DOI: 10.1016/j.biopsych.2006.06.012.
- A limited number of genes are involved in the differentiation of germinal center B cellsNakayama Y, Stabach P, Maher SE, Mahajan MC, Masiar P, Liao C, Zhang X, Ye Z, Tuck D, Bothwell AL, Newburger PE, Weissman SM. A limited number of genes are involved in the differentiation of germinal center B cells. Journal Of Cellular Biochemistry 2006, 99: 1308-1325. PMID: 16795035, DOI: 10.1002/jcb.20952.
- The mutant leucine-zipper domain impairs both dimerization and suppressive function of Foxp3 in T cellsChae WJ, Henegariu O, Lee SK, Bothwell AL. The mutant leucine-zipper domain impairs both dimerization and suppressive function of Foxp3 in T cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 9631-9636. PMID: 16769892, PMCID: PMC1480458, DOI: 10.1073/pnas.0600225103.
- B cells and osteoblast and osteoclast developmentHorowitz MC, Bothwell AL, Hesslein DG, Pflugh DL, Schatz DG. B cells and osteoblast and osteoclast development. Immunological Reviews 2005, 208: 141-153. PMID: 16313346, DOI: 10.1111/j.0105-2896.2005.00328.x.
- Osteoporosis with increased osteoclastogenesis in hematopoietic cell-specific STAT3-deficient miceZhang Z, Welte T, Troiano N, Maher SE, Fu XY, Bothwell AL. Osteoporosis with increased osteoclastogenesis in hematopoietic cell-specific STAT3-deficient mice. Biochemical And Biophysical Research Communications 2005, 328: 800-807. PMID: 15694417, DOI: 10.1016/j.bbrc.2005.01.019.
- Pax5-Deficient Mice Exhibit Early Onset Osteopenia with Increased Osteoclast ProgenitorsHorowitz MC, Xi Y, Pflugh DL, Hesslein DG, Schatz DG, Lorenzo JA, Bothwell AL. Pax5-Deficient Mice Exhibit Early Onset Osteopenia with Increased Osteoclast Progenitors. The Journal Of Immunology 2004, 173: 6583-6591. PMID: 15557148, DOI: 10.4049/jimmunol.173.11.6583.
- Inhibition of alloresponse by a human trophoblast non-coding RNA suppressing class II transactivator promoter III and major histocompatibility class II expression in murine B-lymphocytesGeirsson A, Bothwell AL, Hammond GL. Inhibition of alloresponse by a human trophoblast non-coding RNA suppressing class II transactivator promoter III and major histocompatibility class II expression in murine B-lymphocytes. The Journal Of Heart And Lung Transplantation 2004, 23: 1077-1081. PMID: 15454174, DOI: 10.1016/j.healun.2004.07.020.
- Bcl-2 Transduction Protects Human Endothelial Cell Synthetic Microvessel Grafts from Allogeneic T Cells In VivoZheng L, Gibson TF, Schechner JS, Pober JS, Bothwell AL. Bcl-2 Transduction Protects Human Endothelial Cell Synthetic Microvessel Grafts from Allogeneic T Cells In Vivo. The Journal Of Immunology 2004, 173: 3020-3026. PMID: 15322161, DOI: 10.4049/jimmunol.173.5.3020.
- Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor ζ chain ITAMs and their tyrosine residuesChae WJ, Lee HK, Han JH, Kim SW, Bothwell AL, Morio T, Lee SK. Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor ζ chain ITAMs and their tyrosine residues. International Immunology 2004, 16: 1225-1236. PMID: 15302845, DOI: 10.1093/intimm/dxh120.
- B cell–specific loss of histone 3 lysine 9 methylation in the VH locus depends on Pax5Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K. B cell–specific loss of histone 3 lysine 9 methylation in the VH locus depends on Pax5. Nature Immunology 2004, 5: 853-861. PMID: 15258579, PMCID: PMC1635547, DOI: 10.1038/ni1099.
- Evidence for a dual pathway of activation in CD43-stimulated Th2 cells: differential requirement for the Lck tyrosine kinaseFernandez-Cabezudo MJ, Vijayasarathy C, Pflugh DL, Bothwell AL, al-Ramadi BK. Evidence for a dual pathway of activation in CD43-stimulated Th2 cells: differential requirement for the Lck tyrosine kinase. International Immunology 2004, 16: 1215-1223. PMID: 15237112, DOI: 10.1093/intimm/dxh124.
- Interferon α but Not Interleukin 12 Activates STAT4 Signaling in Human Vascular Endothelial Cells*Torpey N, Maher SE, Bothwell AL, Pober JS. Interferon α but Not Interleukin 12 Activates STAT4 Signaling in Human Vascular Endothelial Cells*. Journal Of Biological Chemistry 2004, 279: 26789-26796. PMID: 15087447, DOI: 10.1074/jbc.m401517200.
- Engraftment of a vascularized human skin equivalentSchechner JS, Crane SK, Wang F, Szeglin AM, Tellides G, Lorber MI, Bothwell AL, Pober JS. Engraftment of a vascularized human skin equivalent. The FASEB Journal 2003, 17: 2250-2256. PMID: 14656987, DOI: 10.1096/fj.03-0257com.
- Receptor Activator of NF-κB Ligand Stimulates Recruitment of SHP-1 to the Complex Containing TNFR-Associated Factor 6 That Regulates OsteoclastogenesisZhang Z, Jimi E, Bothwell AL. Receptor Activator of NF-κB Ligand Stimulates Recruitment of SHP-1 to the Complex Containing TNFR-Associated Factor 6 That Regulates Osteoclastogenesis. The Journal Of Immunology 2003, 171: 3620-3626. PMID: 14500659, DOI: 10.4049/jimmunol.171.7.3620.
- Immunopathology of human T cell responses to skin, artery and endothelial cell grafts in the human peripheral blood lymphocyte/severe combined immunodeficient mousePober JS, Bothwell AL, Lorber MI, McNiff JM, Schechner JS, Tellides G. Immunopathology of human T cell responses to skin, artery and endothelial cell grafts in the human peripheral blood lymphocyte/severe combined immunodeficient mouse. Seminars In Immunopathology 2003, 25: 167-180. PMID: 12955465, DOI: 10.1007/s00281-003-0135-1.
- Class II transactivator promoter activity is suppressed through regulation by a trophoblast noncoding RNA1Geirsson A, Paliwal I, Lynch RJ, Bothwell AL, Hammond GL. Class II transactivator promoter activity is suppressed through regulation by a trophoblast noncoding RNA1. Transplantation 2003, 76: 387-394. PMID: 12883198, DOI: 10.1097/01.tp.0000073612.04525.46.
- STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunityWelte T, Zhang SS, Wang T, Zhang Z, Hesslein DG, Yin Z, Kano A, Iwamoto Y, Li E, Craft JE, Bothwell AL, Fikrig E, Koni PA, Flavell RA, Fu XY. STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2003, 100: 1879-1884. PMID: 12571365, PMCID: PMC149927, DOI: 10.1073/pnas.0237137100.
- Human trophoblast noncoding RNA suppresses CIITA promoter III activity in murine B-lymphocytesGeirsson A, Lynch RJ, Paliwal I, Bothwell AL, Hammond GL. Human trophoblast noncoding RNA suppresses CIITA promoter III activity in murine B-lymphocytes. Biochemical And Biophysical Research Communications 2003, 301: 718-724. PMID: 12565840, DOI: 10.1016/s0006-291x(03)00028-7.
- Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segmentsHesslein DG, Pflugh DL, Chowdhury D, Bothwell AL, Sen R, Schatz DG. Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments. Genes & Development 2003, 17: 37-42. PMID: 12514097, PMCID: PMC195966, DOI: 10.1101/gad.1031403.
- Porcine Endothelial Cells, Unlike Human Endothelial Cells, Can Be Killed by Human CTL Via Fas Ligand and Cannot Be Protected by Bcl-2Zheng L, Ben LH, Pober JS, Bothwell AL. Porcine Endothelial Cells, Unlike Human Endothelial Cells, Can Be Killed by Human CTL Via Fas Ligand and Cannot Be Protected by Bcl-2. The Journal Of Immunology 2002, 169: 6850-6855. PMID: 12471117, DOI: 10.4049/jimmunol.169.12.6850.
- Ly-6 Superfamily Members Ly-6A/E, Ly-6C, and Ly-6I Recognize Two Potential Ligands Expressed by B LymphocytesPflugh DL, Maher SE, Bothwell AL. Ly-6 Superfamily Members Ly-6A/E, Ly-6C, and Ly-6I Recognize Two Potential Ligands Expressed by B Lymphocytes. The Journal Of Immunology 2002, 169: 5130-5136. PMID: 12391229, DOI: 10.4049/jimmunol.169.9.5130.
- Interferon-γ Augments CD95(APO-1/Fas) and Pro-Caspase-8 Expression and Sensitizes Human Vascular Endothelial Cells to CD95-Mediated ApoptosisLi JH, Kluger MS, Madge LA, Zheng L, Bothwell AL, Pober JS. Interferon-γ Augments CD95(APO-1/Fas) and Pro-Caspase-8 Expression and Sensitizes Human Vascular Endothelial Cells to CD95-Mediated Apoptosis. American Journal Of Pathology 2002, 161: 1485-1495. PMID: 12368221, PMCID: PMC1867313, DOI: 10.1016/s0002-9440(10)64424-0.
- Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis inductionShim JH, Lee HK, Chang EJ, Chae WJ, Han JH, Han DJ, Morio T, Yang JJ, Bothwell A, Lee SK. Immunosuppressive effects of tautomycetin in vivo and in vitro via T cell-specific apoptosis induction. Proceedings Of The National Academy Of Sciences Of The United States Of America 2002, 99: 10617-10622. PMID: 12149481, PMCID: PMC124991, DOI: 10.1073/pnas.162522099.
- Cutting Edge: Internalization of Transduced E-Selectin by Cultured Human Endothelial Cells: Comparison of Dermal Microvascular and Umbilical Vein Cells and Identification of a Phosphoserine-Type Di-leucine MotifKluger MS, Shiao SL, Bothwell AL, Pober JS. Cutting Edge: Internalization of Transduced E-Selectin by Cultured Human Endothelial Cells: Comparison of Dermal Microvascular and Umbilical Vein Cells and Identification of a Phosphoserine-Type Di-leucine Motif. The Journal Of Immunology 2002, 168: 2091-2095. PMID: 11859093, DOI: 10.4049/jimmunol.168.5.2091.
- Porcine endothelial CD86 is a major costimulator of xenogeneic human T cells: cloning, sequencing, and functional expression in human endothelial cells.Maher SE, Karmann K, Min W, Hughes CC, Pober JS, Bothwell AL. Porcine endothelial CD86 is a major costimulator of xenogeneic human T cells: cloning, sequencing, and functional expression in human endothelial cells. The Journal Of Immunology 1996, 157: 3838-44. PMID: 8892613, DOI: 10.4049/jimmunol.157.9.3838.