한빛사논문
- 조회2,147
Abstract
Sun Jung Kim1, Yong Rui Zou1, Jordan Goldstein1, Boris Reizis2, and Betty Diamond1
1Center for Autoimmune and Musculoskeletal Diseases, the Feinstein Institute for Medical Research, Manhasset, NY 11030
2Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032
CORRESPONDENCE Betty Diamond
Abstract
Blimp-1 has been identified as a key regulator of plasma cell differentiation in B cells and effector/memory function in T cells. We demonstrate that Blimp-1 in dendritic cells (DCs) is required to maintain immune tolerance in female but not male mice. Female mice lacking Blimp-1 expression in DCs (DCBlimp-1ko) or haploid for Blimp-1 expression exhibit normal DC development but an altered DC function and develop lupus-like autoantibodies. Although DCs have been implicated in the pathogenesis of lupus, a defect in DC function has not previously been shown to initiate the disease process. Blimp-1ko DCs display increased production of IL-6 and preferentially induce differentiation of follicular T helper cells (TFH cells) in vitro. In vivo, the expansion of TFH cells is associated with an enhanced germinal center (GC) response and the development of autoreactivity. These studies demonstrate a critical role for Blimp-1 in the tolerogenic function of DCs and show that a diminished expression of Blimp-1 in DCs can result in aberrant activation of the adaptive immune system with the development of a lupus-like serology in a gender-specific manner. This study is of particular interest because a polymorphism of Blimp-1 associates with SLE.
논문정보
- Research article
- 2011년 09월 (BRIC 등록일 )
- 국외 연구진
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