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Publication : Role of SIRPα in regulation of mucosal immunity in the intestine.

First Author  Kanazawa Y Year  2010
Journal  Genes Cells Volume  15
Issue  12 Pages  1189-200
PubMed ID  21040253 Mgi Jnum  J:186324
Mgi Id  MGI:5432046 Doi  10.1111/j.1365-2443.2010.01453.x
Citation  Kanazawa Y, et al. (2010) Role of SIRPalpha in regulation of mucosal immunity in the intestine. Genes Cells 15(12):1189-200
abstractText  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 alpha (SIRPalpha) is a transmembrane protein that is specifically expressed in DCs, macrophages and neutrophils. Here, we show that SIRPalpha is abundant in CD11c(+) CD11b(+) LP cells of the mouse intestine. Whereas SIRPalpha 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)-gamma by LP cells of SIRPalpha 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 SIRPalpha MT mice was also greatly reduced. SIRPalpha MT mice were also resistant to the development of colitis induced by IL-10 deficiency. Our data thus suggest that SIRPalpha expressed on CD11c(+) LP cells is important for the production of IL-17 or IFN-gamma in the LP as well as for the development of colitis induced by IL-10 deficiency.
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