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

Datu Respatika, Yasuyuki Saito, Ken Washio, Satomi Komori, Takenori Kotani, Hideki Okazawa, Yoji Murata, Takashi Matozaki
2017 Kobe J. Med. Sci   unpublished
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
more » ... ice. 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 Sirpa f/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.