Joseph Edgar Craft, MD

Paul B. Beeson Professor of Medicine (Rheumatology) and Professor of Immunobiology; Section Chief, Rheumatology; Program Director, Investigative Medicine; Paul B. Beeson Professor of Medicine

Research Interests

Antigens, Differentiation, T-Lymphocyte; Autoimmune Diseases; Biology; Immunity; Lupus Erythematosus, Systemic; Investigative Techniques; Rheumatology; Cytokines

Research Organizations

Internal Medicine: Rheumatology

Immunobiology: HTI

Cancer Center: Cancer Immunology

Immunology and Immunotherapy

Office of Cooperative Research

Research Summary

We have a longstanding interest in dissecting the pathogenesis of systemic autoimmunity, focusing upon the activation and differentiation of CD4 T effector cell subsets in mice and in humans. Our lab has characterized CD4 T cells that help B cells in murine models of lupus and in conventional immune responses, with the idea that information gleaned from the latter studies could be applied to our understanding of autoimmunity. In recent work, we have begun to define the transcription factors critical for the development and function of CD4 T cells that help B cells, with ongoing studies aimed at further investigating these cells developmentally, and dissecting the mechanisms that lead to their effector function in autoimmunity and inflammation.

Specialized Terms: Autoimmunity; Cytokines; Lupus; T Cell Differentiation; Tolerance

Extensive Research Description

Ongoing studies are targeted towards identification of the developmental pathways of CD4 T cells that provide B cell help and that promote inflammation, and dissection of their potential to promote autoimmunity and inflammation.

Selected Publications

  • Odegard J, Marks B, Eardley L, Poholek A, Kono D, Dong C, Favell R, Craft J. 2008. ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity. J Exp Med. 205:2873-2886. PMCID: PMC2585848
  • Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Johnson RJ*, Poholek AC*, Yusuf I, DiToro D, Eto D, Barnett B, Dent AL, Craft J, Crotty S. (2009). Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.
  • Marks BR, Nowyhed H, Choi J-Y, Poholek AC, Odegard J, Flavell RA, Craft J. 2009. Thymic self-reactivity selects natural interleukin 17–producing T cells that can regulate peripheral inflammation. Nat Immunol. 10:1125-1132. PMCID: PMC2751862. (Accompanied by News and Views article entitled “The importance of being earnestly selfish” by Cheroutre H, Mucida D & Lambolez F, published in the same issue.) Also see Corrigendum, Nature Immunol. 2010. 11:97.
  • Odegard J, DiPlacido L, Greenwald L, Kashgarian M, Dong C, Flavell R, Craft J. 2009. ICOS controls effector function, but not trafficking receptor expression, of kidney-infiltrating effector T cells in murine lupus. J Immunol. 182:4076-4084. PMCID: PMC2746004
  • Poholek AC and Craft J. Competing for help: New insights into the function of follicular helper T cells. (News and Commentary; invited). Immunol Cell Biol. 87:438-439. 2009.
  • In vivo regulation of Bcl6 and T follicular helper cell development. Poholek AC, Hansen K, Hernandez S, Eto D, Chandele A, Weinstein J, Dong X, Odegard JM, Kaech SM, Dent AL, Crotty S, Craft J. (2010) In vivo regulation of Bcl6 and T follicular helper cell development.
  • DiPlacido L, Craft J. Emerging from the shadows: follicular helper T cells in autoimmunity (Editorial, invited). Arth Rheum. 62:6–8, 2010. PMCID: PMC2806501
  • Differential expression of Ly6C and T-bet distinguish effector and memory Th1 CD4(+) cell properties during viral infection. Marshall HD, Chandele A, Jung YW, Meng H, Poholek AC, Parish IA, Rutishauser R, Cui W, Kleinstein SH, Craft J, Kaech SM. (2011) Differential expression of Ly6C and T-bet distinguish effector and memory Th1 CD4(+) cell properties during viral infection.
  • Cui W, Yiu L, Weinstein J, Craft J, Kaech SM. An IL-21/IL-10/STAT3 pathway is critical for functional maturation of memory CD8+ T cells. Immunity. 35:792-805, 2011. PMCID: PMC3431922
  • Choi JY, Kim ST, Craft J. The pathogenesis of SLE: An Update. Curr Opin Immunol. 24:651-657, 2012. PMCID: PMC3508331
  • Weinstein JS, Hernandez SG, Craft J. T cells that promote B-Cell maturation in systemic autoimmunity. Immunol Rev. 247:160-171. 2012. PMCID: PMC3334351
  • Look M, Stern E, Wan Q, DiPlacido LD, Kashgarian M, Craft J, and Fahmy TM. Nanogel-based delivery of mycophenolic acid ameliorates systemic lupus erythematosus in mice. J Clin Invest. 123:1741-1749, 2013. PMCID: PMC3613921
  • Bertino SA and Craft J. Roquin Paralogs Add a New Dimension to ICOS Regulation. Immunity 38:624-626, 2013. PMCID: PMC3786165
  • Kumamoto Y, Lineham M, Weinstein J, Laidlaw B, Craft J, Iwasaki A. CD301b+ dermal dendritic cells drive TH2 cell-mediated immunity. Immunity. 39:733-74, 2013. PMCID: PMC3819035
  • Ray JP, Marshall HD, Laidlaw BJ, Staron MW, Kaech SM, Craft J. 2014. The transcription factor STAT3 and type I Interferons are mutually repressive insulators for differentiation of follicular helper and T helper 1 cells. Immunity. 40:367-377. PMCID: PMC3992517 (Accompanied by a Perspectives article entitled “Tfh cell differentiation: Missing Stat3 uncovers interferons’ interference” by Edelmann SL and Heissmeyer V, published in the same issue.)
  • Weinstein J, Bertino SA, Hernandez SG, Poholek AC, Teplitzky TB, Nowyhed HN, Craft J. 2014. B cells in T follicular helper cell development and function: Separable roles in delivery of ICOS ligand and antigen. J Immunol. 192:3166-3179. PMCID: PMC3991608
  • Shulman Z, Gitlin AD, Weinstein JS, Lainez B, Esplugues E, Flavell RA, Craft J, Nussenzweig M. 2014. Dynamic signaling by T follicular helper cells during germinal center B cell selection. Science. 345:1058-1062. PMCID: PMC4519234
  • Weinstein JS, Lezon-Geyda K, Maksimova Y, Craft S, Zhang Y, Su M, Schultz VP, Craft J*, Gallagher PG*. 2014. Global transcriptome analysis and enhancer landscape of human primary T follicular helper and T effector lymphocytes. Blood. 124:3719-3729 (*co-senior and co-corresponding authors). PMCID: PMC4263981
  • Laidlaw BJ, Zhang N, Marshall HD, Staron MM, Guan T, Hu Y, Cauley LS, Craft J*, Kaech SM*. 2014. CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection. Immunity. 41:633-645. (*co-senior and co-corresponding authors). (Accompanied by a Perspectives article entitled “CD4 helpers put tissue-resident memory cells in their Place” by Mackay LK & Carbone FR, published in the same issue.) PMCID: PMC5324721
  • Laidlaw BJ, Cui W, Amezquita R, Gray SM, Guan T, Lu Y, Kobayashi Y, Flavell RA, Kleinstein S, Craft J*, Kaech SM*. 2015. IL-10 production by regulatory CD4+ T cells during resolution of infection promotes memory CD8+ T cell maturation. Nature Immunol 10.1038/ni.3224 (*co-senior and co-corresponding authors).
  • Choi JY, Ho JH, Pasoto SG, Bunin V, Kim ST, Carrasco S, Borba EF, Gonçalves CR, Costa PR, Esper GK, Bonfa E*, Craft J*. 2015. Circulating follicular helper-like T cells in systemic lupus erythematosus: Association with disease activity. Arth Rheum. 67:988–999. (*co-senior and co-corresponding authors). PMCID: PMC4450082
  • Ray JP and Craft J. PTENtiating autoimmunity through Treg deregulation. Nat Immunol. 16(2):139-40. 2015. PMCID: PMC4447107
  • Marshall HD, Ray JP, Laidlaw BJ, Zhang N, Gawande D, Staron MM, Craft J, Kaech SM. The tumor growth factor beta signaling pathway is critical for the formation of CD4 T follicular helper cells and isotype-switched antibody responses in the lung mucosa. eLife. 2015. PMCID: PMC4337607
  • Teichmann LL, Cullen JL, Kashgarian M, Dong C, Craft J, Shlomchik MJ. Local triggering of the ICOS coreceptor by CD11c(+) myeloid cells drives organ inflammation in lupus. Immunity. 2015. PMCID: PMC4456685
  • Ray JR, Staron MM, Shyer JA, Ho P-C, Marshall HD, Gray SM, Laidlaw BJ, Araki K, Ahmed R, Kaech SM*, Craft J*. The interleukin-2/mTORc1 axis designates the reciprocal signaling, differentiation, and metabolism of T helper 1 and follicular helper T cells. Immunity (in press). (*co-senior and co-corresponding authors)
  • Dissecting the immune cell mayhem that drives lupus pathogenesis. Craft JE1. (2011) Dissecting the immune cell mayhem that drives lupus pathogenesis.
  • Laidlaw BL, Craft J, Kaech SM. Multifaceted role of CD4+ T cells in the regulation of CD8+ T cell memory maturation. Nature Reviews Immunology doi:10.1038/nri.2015.10; Published online 19 Jan 2016.
  • Weinstein JS*, Herman EI*, Lainez B*, Licona-Limón P, Esplugues E, Flavell RA, and Craft J. TFH cells progressively differentiate to regulate the germinal center response. Nature Immunology 10.1038/ni.3554. *Joint first authors.

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Contact Info

Joseph Edgar Craft, MD
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Yale Investigative MedicineLippard Lab for Clinical Investigation
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New Haven, CT 06510
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Yale RheumatologyYale-New Haven Hospital
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