The transcription factor RelB restrains group 2 innate lymphoid cells and type 2 immune pathology in vivo

Lei Zhang, Yuanlin Ying, Shuqiu Chen, Preston R. Arnold, Fafa Tian, Laurie J. Minze, Xiang Xiao, Xian C. Li

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

The exact relationships between group 2 innate lymphoid cells (ILC2s) and Th2 cells in type 2 pathology, as well as the mechanisms that restrain the responses of these cells, remain poorly defined. Here we examined the roles of ILC2s and Th2 cells in type 2 lung pathology in vivo using germline and conditional Relb-deficient mice. We found that mice with germline deletion of Relb (Relb−/−) spontaneously developed prominent type 2 pathology in the lung, which contrasted sharply with mice with T-cell-specific Relb deletion (Relbf/fCd4-Cre), which were healthy with no observed autoimmune pathology. We also found that in contrast to wild-type B6 mice, Relb-deficient mice showed markedly expanded ILC2s but not ILC1s or ILC3s. Moreover, adoptive transfer of naive CD4+ T cells into Rag1−/−Relb−/− hosts induced prominent type 2 lung pathology, which was inhibited by depletion of ILC2s. Mechanistically, we showed that Relb deletion led to enhanced expression of Bcl11b, a key transcription factor for ILC2s. We concluded that RelB plays a critical role in restraining ILC2s, primarily by suppressing Bcl11b activity, and consequently inhibits type 2 lung pathology in vivo.

Original languageEnglish (US)
Pages (from-to)230-242
Number of pages13
JournalCellular and Molecular Immunology
Volume18
Issue number1
DOIs
StatePublished - Jan 2021

Keywords

  • Allergic inflammation
  • Innate lymphoid cells
  • NF-κB
  • RelB
  • Th2 cells
  • type 2 pathology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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