CD38 Deficiency Ameliorates Chronic Graft- Versus-Host Disease Murine Lupus via a B-Cell-Dependent Mechanism
Keywords:CD38; GC B cells; STAT1; T-bet+ B cells; anti-ssDNA antibodies; cGVHD lupus-like; inflammation; type I IFN-signature.- Front Immunol
- 8.786
- 2021 Aug 24:12:713697.
- Mouse
- Luminex
- B细胞
- IL-17F,IL-21,IL-22,IL-23,IL-25 (IL-17E),IL-27,IL-31,IL-33,CD40L,MIP-3α
相关货号
LXLBM10-2
Abstract
The absence of the mouse cell surface receptor CD38 in Cd38-/- mice suggests that this receptor acts as a positive regulator of inflammatory and autoimmune responses. Here, we report that, in the context of the chronic graft-versus-host disease (cGVHD) lupus inducible model, the transfer of B6.C-H2bm12/KhEg(bm12) spleen cells into co-isogenic Cd38-/- B6 mice causes milder lupus-like autoimmunity with lower levels of anti-ssDNA autoantibodies than the transfer of bm12 spleen cells into WT B6 mice. In addition, significantly lower percentages of Tfh cells, as well as GC B cells, plasma cells, and T-bet+CD11chi B cells, were observed in Cd38-/- mice than in WT mice, while the expansion of Treg cells and Tfr cells was normal, suggesting that the ability of Cd38-/- B cells to respond to allogeneic help from bm12 CD4+ T cells is greatly diminished. The frequencies of T-bet+CD11chi B cells, which are considered the precursors of the autoantibody-secreting cells, correlate with anti-ssDNA autoantibody serum levels, IL-27, and sCD40L. Proteomics profiling of the spleens from WT cGVHD mice reflects a STAT1-driven type I IFN signature, which is absent in Cd38-/- cGVHD mice. Kidney, spleen, and liver inflammation was mild and resolved faster in Cd38-/- cGVHD mice than in WT cGVHD mice. We conclude that CD38 in B cells functions as a modulator receptor that controls autoimmune responses.
Keywords:CD38; GC B cells; STAT1; T-bet+ B cells; anti-ssDNA antibodies; cGVHD lupus-like; inflammation; type I IFN-signature.
Keywords:CD38; GC B cells; STAT1; T-bet+ B cells; anti-ssDNA antibodies; cGVHD lupus-like; inflammation; type I IFN-signature.
金课堂之文献解析 文献原文请点击
本网站销售的所有产品及服务均不得用于人类或动物之临床诊断或治疗,仅可用于工业或者科研等非医疗目的。