Deficiency of scavenger receptor BI leads to impaired lymphocyte homeostasis and autoimmune disorders in mice

Hong Feng, Ling Guo, Dan Wang, Haiqing Gao, Guihua Hou, Zhong Zheng, Junting Ai, Oded Foreman, Alan Daugherty, Xiang An Li

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Objective-: Scavenger receptor BI (SR-BI) is a high-density lipoprotein (HDL) receptor. Recent studies revealed that SR-BI protects against sepsis via modulating innate immunity. However, its role in adaptive immunity is unclear. Methods and Results-: SR-BI-null mice exhibited impaired lymphocyte homeostasis as shown by splenomegaly and imbalanced expansion of T and B lymphocytes in the spleens. Importantly, the activated T and B lymphocytes were increased 3-to 4-fold, indicating a heightened active status of T and B lymphocytes. More importantly, in line with the accumulation of the activated T and B lymphocytes, SR-BI-null mice developed systemic autoimmune disorders characterized by the presence of autoantibodies in circulation, the deposition of immune complexes in glomeruli, and the leukocyte infiltration in kidney. Further analyses revealed that SR-BI deficiency enhanced lymphocyte proliferation, caused imbalanced interferon-γ and interleukin-4 production in lymphocytes, and caused elevated inflammatory cytokine production in macrophages. Furthermore, HDL from SR-BI-null mice exhibited less capability of suppressing lymphocyte proliferation. Conclusion-: SR-BI regulates lymphocyte homeostasis, likely through its roles in modulating the proliferation of lymphocytes, the cytokine production by lymphocytes and macrophages, and the function of HDL. Its deficiency leads to impaired lymphocyte homeostasis and autoimmune disorders. Our findings reveal a previously unrecognized role of SR-BI in adaptive immunity.

Original languageEnglish
Pages (from-to)2543-2551
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number11
DOIs
StatePublished - Nov 2011

Keywords

  • HDL
  • SR-BI
  • Scarb1
  • adaptive immunity
  • lipoproteins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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