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Joao Pereira, PhD

Associate Professor of Immunobiology

Contact Information

Joao Pereira, PhD

Lab Location

Mailing Address

  • Immunobiology

    The Anlyan Center, 300 Cedar Street

    New Haven, CT 06519

    United States

Pereira Lab

Research Summary

Research in this laboratory is focused on several aspects related to B cell biology, a fundamental player of adaptive immunity. B cells develop from hematopoietic stem cells (HSCs) in specialized microenvironments in the bone marrow, named stem cell niches that are also critical for the maintenance and differentiation of HSCs and of hematopoietic multipotent progenitor cells (MPPs). Besides nurturing B cells, HSCs, and MPPs, bone marrow stem cell niches seem also to be important for controlling adaptive immunity. Antibody producing plasma cells and memory T cells travel from sites of activation and differentiation (mostly, secondary lymphoid organs) back to bone marrow stem cell niches for receiving important cytokine signals that enable their long-term survival. Our laboratory is specifically interested in understanding the molecular cross-talk between HSCs, MPPs, B cells, etc. and stem cell niche cells. Our long-term goals are to make impactful discoveries on the basic understanding of immune cell development, differentiation, and regulation, and in this process reveal novel therapeutic targets and/or strategies for treating B cell-mediated autoimmune diseases, malignancies, or immune deficiencies. Work in this laboratory is in frequent interaction with investigators in the Yale Cancer Center and Yale Stem Cell Center.

Specialized Terms: Immunology; Hematopoiesis; B-lymphocyte development; Bone marrow niches; Cell migration

Extensive Research Description

Active areas of research

1- Bone marrow Stem Cell niches

All blood cells develop from hematopoietic stem cells (HSC) through complex developmental transitions that require cell-lineage instructive transcription factors and cell-extrinsic lineage-instructive cytokines. Stem cell niches are key organizers of HSC maintenance and differentiation due to their capacity to produce cytokines (e.g. Stem Cell Factor, IL-7, IL-15, etc.) and chemokines (e.g. CXCL12). Stem cell niches are formed predominantly by a relatively rare population of mesenchymal stem/progenitor cells (MSPCs) that expresses Leptin receptor and PDGFRs. Importantly, MSPCs either reduce or loose the ability to express niche cytokines upon differentiation into mesenchymal-lineage cells such as adipocytes, osteoblasts, chondrocytes. These observations suggest that cytokine production by MSPCs is regulated by short and/or long-range signals, but these mechanisms are largely unknown. Also poorly understood is the physiological role of MSPCs in the long-term maintenance of antibody-secreting plasma cells.



2- Where and how B cell development occurs in vivo.

B cell precursors switch from non-motile and highly adherent states (proB cell stage) to highly motile and less adherent states (preB cell stage). As a consequence, the time these two distinct B cell subsets spend in contact with IL-7 producing MSPCs is remarkably different and highly regulated. This type of change in dynamic behavior suggests that cross-talk between proB, preB, and MSPCs is important for the quality and possibly quantity of B cells being produced. This is a highly exciting area of research that is likely to have a major impact in our understanding of how pre-leukemic and leukemic B cell progenitors change the bone marrow microenvironment.


3- Chemoattractants, receptors, and B cell homeostasis.

Immune cells are highly organized in primary and secondary lymphoid organs. B cells and T cells occupy distinct areas of the spleen and lymph nodes due to the differential expression of chemoattractant receptors. Chemoattractants act as ZIP codes for immune cells to know where they should be located. However, chemoattractant receptor signaling does more to cells than simply inform them of where they are or where they should go. By taking advantage of one of nature’s tools, Pertussis toxin, we are currently investigating the physiological impact of blocked chemoattractant receptor signaling in the development and maintenance of B cells.


Coauthors

Research Interests

B-Lymphocytes; Bone Marrow; Hematopoiesis; Hematopoietic Stem Cells; Immune System; Stromal Cells

Selected Publications

  • Cell circuits between B cell progenitors and IL-7+ mesenchymal progenitor cells control B cell development.Fistonich C, Zehentmeier S, Bednarski JJ, Miao R, Schjerven H, Sleckman BP, Pereira JP. Cell circuits between B cell progenitors and IL-7+ mesenchymal progenitor cells control B cell development. The Journal Of Experimental Medicine 2018, 215: 2586-2599. PMID: 30158115, PMCID: PMC6170173, DOI: 10.1084/jem.20180778.
  • A Chemoattractant-Guided Walk Through Lymphopoiesis: From Hematopoietic Stem Cells to Mature B Lymphocytes.Lim VY, Zehentmeier S, Fistonich C, Pereira JP. A Chemoattractant-Guided Walk Through Lymphopoiesis: From Hematopoietic Stem Cells to Mature B Lymphocytes. Advances In Immunology 2017, 134: 47-88. PMID: 28413023, PMCID: PMC5784265, DOI: 10.1016/bs.ai.2017.02.001.
  • Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation.Cordeiro Gomes A, Hara T, Lim VY, Herndler-Brandstetter D, Nevius E, Sugiyama T, Tani-Ichi S, Schlenner S, Richie E, Rodewald HR, Flavell RA, Nagasawa T, Ikuta K, Pereira JP. Hematopoietic Stem Cell Niches Produce Lineage-Instructive Signals to Control Multipotent Progenitor Differentiation. Immunity 2016, 45: 1219-1231. PMID: 27913094, PMCID: PMC5538583, DOI: 10.1016/j.immuni.2016.11.004.
  • Inflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review.Nevius E, Gomes AC, Pereira JP. Inflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review. Clinical Reviews In Allergy & Immunology 2016, 51: 59-78. PMID: 26511861, PMCID: PMC5785098, DOI: 10.1007/s12016-015-8520-9.
  • Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis.Nevius E, Pinho F, Dhodapkar M, Jin H, Nadrah K, Horowitz MC, Kikuta J, Ishii M, Pereira JP. Oxysterols and EBI2 promote osteoclast precursor migration to bone surfaces and regulate bone mass homeostasis. The Journal Of Experimental Medicine 2015, 212: 1931-46. PMID: 26438360, PMCID: PMC4612084, DOI: 10.1084/jem.20150088.
  • Immature B Cell Egress from Bone Marrow Is SOCS3 Independent.Nadrah K, Beck TC, Pereira JP. Immature B Cell Egress from Bone Marrow Is SOCS3 Independent. PloS One 2015, 10: e0136061. PMID: 26274929, PMCID: PMC4537204, DOI: 10.1371/journal.pone.0136061.
  • CXCR4 and a cell-extrinsic mechanism control immature B lymphocyte egress from bone marrow.Beck TC, Gomes AC, Cyster JG, Pereira JP. CXCR4 and a cell-extrinsic mechanism control immature B lymphocyte egress from bone marrow. The Journal Of Experimental Medicine 2014, 211: 2567-81. PMID: 25403444, PMCID: PMC4267240, DOI: 10.1084/jem.20140457.
  • Oxysterols direct immune cell migration via EBI2.Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D, Pereira JP, Guerini D, Baumgarten BU, Roggo S, Wen B, Knochenmuss R, Noël S, Gessier F, Kelly LM, Vanek M, Laurent S, Preuss I, Miault C, Christen I, Karuna R, Li W, Koo DI, Suply T, Schmedt C, Peters EC, Falchetto R, Katopodis A, Spanka C, Roy MO, Detheux M, Chen YA, Schultz PG, Cho CY, Seuwen K, Cyster JG, Sailer AW. Oxysterols direct immune cell migration via EBI2. Nature 2011, 475: 524-7. PMID: 21796212, PMCID: PMC4297623, DOI: 10.1038/nature10280.
  • EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and nonlymphoid tissues.Kelly LM, Pereira JP, Yi T, Xu Y, Cyster JG. EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and nonlymphoid tissues. Journal Of Immunology (Baltimore, Md. : 1950) 2011, 187: 3026-32. PMID: 21844396, PMCID: PMC3169736, DOI: 10.4049/jimmunol.1101262.
  • A role for S1P and S1P1 in immature-B cell egress from mouse bone marrow.Pereira JP, Xu Y, Cyster JG. A role for S1P and S1P1 in immature-B cell egress from mouse bone marrow. PloS One 2010, 5: e9277. PMID: 20174580, PMCID: PMC2823786, DOI: 10.1371/journal.pone.0009277.
  • Finding the right niche: B-cell migration in the early phases of T-dependent antibody responses.Pereira JP, Kelly LM, Cyster JG. Finding the right niche: B-cell migration in the early phases of T-dependent antibody responses. International Immunology 2010, 22: 413-9. PMID: 20508253, PMCID: PMC2877811, DOI: 10.1093/intimm/dxq047.
  • EBI2 mediates B cell segregation between the outer and centre follicle.Pereira JP, Kelly LM, Xu Y, Cyster JG. EBI2 mediates B cell segregation between the outer and centre follicle. Nature 2009, 460: 1122-6. PMID: 19597478, PMCID: PMC2809436, DOI: 10.1038/nature08226.
  • Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids.Pereira JP, An J, Xu Y, Huang Y, Cyster JG. Cannabinoid receptor 2 mediates the retention of immature B cells in bone marrow sinusoids. Nature Immunology 2009, 10: 403-11. PMID: 19252491, PMCID: PMC2768754, DOI: 10.1038/ni.1710.
  • T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow.Jenne CN, Enders A, Rivera R, Watson SR, Bankovich AJ, Pereira JP, Xu Y, Roots CM, Beilke JN, Banerjee A, Reiner SL, Miller SA, Weinmann AS, Goodnow CC, Lanier LL, Cyster JG, Chun J. T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow. The Journal Of Experimental Medicine 2009, 206: 2469-81. PMID: 19808259, PMCID: PMC2768857, DOI: 10.1084/jem.20090525.
  • Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate.Pappu R, Schwab SR, Cornelissen I, Pereira JP, Regard JB, Xu Y, Camerer E, Zheng YW, Huang Y, Cyster JG, Coughlin SR. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science (New York, N.Y.) 2007, 316: 295-8. PMID: 17363629, DOI: 10.1126/science.1139221.
  • Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients.Schwab SR, Pereira JP, Matloubian M, Xu Y, Huang Y, Cyster JG. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science (New York, N.Y.) 2005, 309: 1735-9. PMID: 16151014, DOI: 10.1126/science.1113640.
  • Monoallelic expression of the murine gene encoding Toll-like receptor 4.Pereira JP, Girard R, Chaby R, Cumano A, Vieira P. Monoallelic expression of the murine gene encoding Toll-like receptor 4. Nature Immunology 2003, 4: 464-70. PMID: 12665857, DOI: 10.1038/ni917.
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