Macrophage scavenger receptor 1 (Msr1, SR-A) influences B cell autoimmunity by regulating soluble autoantigen concentration.
Macrophage scavenger receptor 1 (Msr1, SR-A) influences B cell autoimmunity by regulating soluble autoantigen concentration.
复制标题
DOI：
10.4049/jimmunol.1201680
复制
发表时间：
2013-08-01
期刊：
影响因子：
--
通讯作者：
Binstadt BA
中科院分区：
文献类型：
--
作者：
Haasken S;Auger JL;Taylor JJ;Hobday PM;Goudy BD;Titcombe PJ;Mueller DL;Binstadt BA
据报道，A类巨噬细胞清道夫受体Msr1 （SR-A, CD204）参与免疫耐受的维持。我们研究了Msr1在自身抗体依赖性关节炎小鼠模型中的作用。在K/BxN TCR转基因小鼠中，由于自身抗体产生减少，Msr1的遗传缺陷降低了关节炎的发病率和严重程度。尽管自身反应性CD4+ T细胞正常初始活化，但Msr1−/−K/BxN小鼠中潜在的自身反应性B细胞保留naïve表型并且不扩增。这不是由于内在的B细胞缺陷。相反，我们发现缺乏Msr1的巨噬细胞在吸收关键的自身抗原葡萄糖-6-磷酸异构酶（GPI）方面效率低下，并且Msr1缺乏的小鼠血清GPI浓度升高。将Msr1−/−K/BxN小鼠的骨髓移植到巨噬细胞表达Msr1的宿主体内后，关节炎发生正常。因此，Msr1可以调节可溶性自身抗原的浓度。在该模型中，Msr1的缺失导致可溶性自身抗原水平升高，并保护小鼠不产生致病性自身抗体，这可能是由于自身反应性T细胞和B细胞的同源相互作用发生改变，滤泡辅助T细胞分化受损。
The class A macrophage scavenger receptor Msr1 (SR-A, CD204) has been reported to participate in the maintenance of immunological tolerance. We investigated the role of Msr1 in a mouse model of autoantibody-dependent arthritis. Genetic deficiency of Msr1 in K/BxN TCR transgenic mice decreased the incidence and severity of arthritis, due to decreased autoantibody production. Despite normal initial activation of autoreactive CD4+ T cells, potentially autoreactive B cells in Msr1−/− K/BxN mice retained a naïve phenotype and did not expand. This was not due to an intrinsic B cell defect. Rather, we found that macrophages lacking Msr1 were inefficient at taking up the key autoantigen glucose-6-phosphate isomerase (GPI) and that Msr1-deficient mice had elevated serum concentrations of GPI. Arthritis developed normally when bone marrow from Msr1−/− K/BxN mice was transplanted into hosts whose macrophages did express Msr1. Thus, Msr1 can regulate the concentration of a soluble autoantigen. In this model, the absence of Msr1 led to higher levels of soluble autoantigen and protected mice from developing pathogenic autoantibodies, likely due to altered cognate interactions of autoreactive T and B cells with impaired differentiation of follicular helper T cells.
登录
查看更多内容
影响因子：
4.4
作者：
Martinez, Ryan J.;Zhang, Na;Mueller, Daniel L.
通讯作者：
Mueller, Daniel L.
影响因子：
--
作者：
Nguyen, Linh T.;Jacobs, Jonathan;Benoist, Christophe
通讯作者：
Benoist, Christophe
影响因子：
9.8
作者：
Lie, BA;Ronningen, KS;Undlien, DE
通讯作者：
Undlien, DE
影响因子：
2.6
作者：
Munoz, L. E.;van Bavel, C.;van der Vlag, J.
通讯作者：
van der Vlag, J.
影响因子：
15.9
作者：
Akilesh, S;Petkova, S;Roopenian, D
通讯作者：
Roopenian, D