Role of SIRPα in Homeostatic Regulation of T Cells and Fibroblastic Reticular Cells in the Spleen

SIRPα 在脾脏 T 细胞和成纤维细胞网状细胞稳态调节中的作用

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作者:Datu Respatika, Yasuyuki Saito, Ken Washio, Satomi Komori, Takenori Kotani, Hideki Okazawa, Yoji Murata, Takashi Matozaki

Abstract

Signal regulatory protein α (SIRPα), is an immunoglobulin superfamily protein that is predominantly expressed in macrophages and dendritic cells (DCs), especially CD4+ conventional DCs (cDCs). In this study, we demonstrated that, in addition to the reduced number of CD4+ cDCs, the number of T cells was significantly decreased in the spleen of Sirpa-/- mice, in which full-length of SIRPα protein was systemically ablated. The size of the T cell zone was markedly reduced in the spleen of Sirpa-/- mice. In addition, Sirpa-/- mice revealed a marked reduction of CCL19, CCL21, and IL-7 expression, which are thought to be important for homeostasis of T cells in the spleen. Consistently, the abundance of fibroblastic reticular cells (FRCs), a subset of stromal cells in the T cell zone, was markedly reduced in the spleen of Sirpa-/- mice compared with Sirpaf/f mice. Moreover, we demonstrated that the mRNA expression of Lymphotoxin (LT) α, LTβ, and LIGHT was significantly reduced in the spleen of Sirpa-/- mice. These data thus suggest that SIRPα is essential for steady-state homeostasis of T cells and FRCs in the spleen.

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