Deficiency of Bim in dendritic cells contributes to overactivation of lymphocytes and autoimmunity.
Apoptosis in dendritic cells (DCs) can potentially regulate DC homeostasis and immune responses. We have previously observed that inhibition of the Fas signaling pathway in DCs results in spontaneous T-cell activation and the development of systemic autoimmunity in transgenic mice. However, the role for different apoptosis pathways in DCs in regulating DC homeostasis and immune tolerance remains to be determined. Bim, a BH3-only protein of the Bcl-2 family, was expressed at low levels in DCs and was significantly up-regulated by signaling from CD40 or toll-like receptors (TLRs). Because Bim(-/-) mice develop spontaneous systemic autoimmunity, we investigated whether Bim(-/-) DCs contributed to lymphoproliferation and autoimmunity in these mice. Bim(-/-) DCs showed decreased spontaneous cell death, and induced more robust T-cell activation in vitro and in vivo. Moreover, Bim(-/-) DCs induced autoantibody production after adoptive transfer. Our data suggest that Bim is important for regulating spontaneous cell death in DCs, and Bim-deficient DCs may contribute to the development of autoimmune diseases in Bim(-/-) mice.
Chen
Min
M
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Huang
Li
L
Wang
Jin
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics*; D000072224:Bcl-2-Like Protein 11; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D001323:Autoantibodies; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins