Deficiency of scavenger receptor BI leads to impaired lymphocyte homeostasis and autoimmune disorders in mice.
Adaptive Immunity, Animals, Autoimmune Diseases, B-Lymphocytes, Cell Proliferation, Disease Models, Animal, Homeostasis, Interferon-gamma, Interleukin-4, Mice, Mice, Knockout, Scavenger Receptors, Class B, Splenomegaly, T-Lymphocytes
Arterioscler Thromb Vasc Biol 2011 Nov; 31(11):2543-51.
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.
Feng, Hong; Guo, Ling; Wang, Dan; Gao, Haiqing; Hou, Guihua; Zheng, Zhong; Ai, Junting; Foreman, Oded; Daugherty, Alan; and Li, Xiang-An, "Deficiency of scavenger receptor BI leads to impaired lymphocyte homeostasis and autoimmune disorders in mice." (2011). Faculty Research 2011. 175.