Role of SIRPα in regulation of mucosal immunity in the intestine

Yoshitake Kanazawa, Yasuyuki Saito, Yana Supriatna, Hiroyuki Tezuka, Takenori Kotani, Yoji Murata, Hideki Okazawa, Hiroshi Ohnishi, Yoshitaka Kinouchi, Yoshihisa Nojima, Toshiaki Ohteki, Tooru Shimosegawa, Takashi Matozaki

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Mononuclear phagocytes such as dendritic cells (DCs) and macrophages in the lamina propria (LP) are thought to be important for both induction of inflammatory responses and maintenance of immunologic tolerance in the mammalian intestine. The molecular mechanisms by which these cells regulate intestinal immunity have remained poorly understood, however. Signal regulatory protein α (SIRPα) is a transmembrane protein that is specifically expressed in DCs, macrophages and neutrophils. Here, we show that SIRPα is abundant in CD11c+ CD11b+ LP cells of the mouse intestine. Whereas SIRPα did not appear to be important for the steady-state homeostasis of mucosal immunity in the intestine, the flagellin-stimulated production of IL-17 or interferon (IFN)-γ by LP cells of SIRPα mutant (MT) mice that lack the cytoplasmic region of the protein was markedly decreased compared with that observed with wild-type cells. Moreover, the flagellin-induced production of IL-6 by LP cells from SIRPα MT mice was also greatly reduced. SIRPα MT mice were also resistant to the development of colitis induced by IL-10 deficiency. Our data thus suggest that SIRPα expressed on CD11c+ LP cells is important for the production of IL-17 or IFN-γ in the LP as well as for the development of colitis induced by IL-10 deficiency.

Original languageEnglish
Pages (from-to)1189-1200
Number of pages12
JournalGenes to Cells
Issue number12
Publication statusPublished - 2010 Dec


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