4.6 Review

NR4A nuclear receptors in T and B lymphocytes: Gatekeepers of immune tolerance

期刊

IMMUNOLOGICAL REVIEWS
卷 307, 期 1, 页码 116-133

出版社

WILEY
DOI: 10.1111/imr.13072

关键词

anergy; B cell tolerance; clonal diversity; immunodominance; negative selection; NOR1; Nr4a1; Nr4a3; NUR77; self-reactivity; T cell tolerance

资金

  1. NIAMS [R01 AR069520]
  2. NIAID [R01 AI148487, R01 AI155653]
  3. Rheumatology Research Foundation
  4. Uehara Memorial Foundation Research Fellowship
  5. AAI Postdoctoral Fellowship
  6. NIGMS Molecular and Cellular Immunology Program [T32AI00733432]
  7. NIAMS Academic Rheumatology and Clinical Immunology Program [T32AR079068]

向作者/读者索取更多资源

This review discusses the important role of the NR4A family of nuclear hormone receptors in immune tolerance and explores the mechanisms by which they regulate self-tolerance and immune homeostasis.
Random VDJ recombination early in T and B cell development enables the adaptive immune system to recognize a vast array of evolving pathogens via antigen receptors. However, the potential of such randomly generated TCRs and BCRs to recognize and respond to self-antigens requires layers of tolerance mechanisms to mitigate the risk of life-threatening autoimmunity. Since they were originally cloned more than three decades ago, the NR4A family of nuclear hormone receptors have been implicated in many critical aspects of immune tolerance, including negative selection of thymocytes, peripheral T cell tolerance, regulatory T cells (Treg), and most recently in peripheral B cell tolerance. In this review, we discuss important insights from many laboratories as well as our own group into the function and mechanisms by which this small class of primary response genes promotes self-tolerance and immune homeostasis to balance the need for host defense against the inherent risks posed by the adaptive immune system.

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