| First Author | Kim SJ | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 11 | Pages | 2193-9 |
| PubMed ID | 21948081 | Mgi Jnum | J:178876 |
| Mgi Id | MGI:5300442 | Doi | 10.1084/jem.20110658 |
| Citation | Kim SJ, et al. (2011) Tolerogenic function of Blimp-1 in dendritic cells. J Exp Med 208(11):2193-9 |
| abstractText | 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-1(ko)) 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-1(ko) DCs display increased production of IL-6 and preferentially induce differentiation of follicular T helper cells (T(FH) cells) in vitro. In vivo, the expansion of T(FH) 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. |
