SIRPα/CD172α regulates eosinophil homeostasis

Noel Verjan Garcia, Eiji Umemoto, Yasuyuki Saito, Mikako Yamasaki, Erina Hata, Takashi Matozaki, Masaaki Murakami, Yun Jae Jung, So Youn Woo, Ju Young Seoh, Myoung Ho Jang, Katsuyuki Aozasa, Masayuki Miyasaka

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Eosinophils are abundant in the lamina propria of the small intestine, but they rarely show degranulation in situ under steady-state conditions. In this study, using two novel mAbs, we found that intestinal eosinophils constitutively expressed a high level of an inhibitory receptor signal regulatory protein α (SIRPα)/CD172a and a low, but significant, level of a tetraspanin CD63, whose upregulation is closely associated with degranulation. Cross-linking SIRPα/CD172a on the surface of wild-type eosinophils significantly inhibited the release of eosinophil peroxidase induced by the calcium ionophore A23187, whereas this cross-linking effect was not observed in eosinophils isolated from mice expressing a mutated SIRPα/CD172a that lacks most of its cytoplasmic domain (SIRPα Cyto-/-). The SIRPα Cyto-/- eosinophils showed reduced viability, increased CD63 expression, and increased eosinophil peroxidase release with or without A23187 stimulation in vitro. In addition, SIRPα Cyto-/- mice showed increased frequencies of Annexin V-binding eosinophils and free MBP +CD63+ extracellular granules, as well as increased tissue remodeling in the small intestine under steady-state conditions. Mice deficient in CD47, which is a ligand for SIRPα/CD172a, recapitulated these phenomena. Moreover, during Th2-biased inflammation, increased eosinophil cell death and degranulation were obvious in a number of tissues, including the small intestine, in the SIRPa Cyto-/- mice compared with wild-type mice. Collectively, our results indicated that SIRPα/CD172a regulates eosinophil homeostasis, probably by interacting with CD47, with substantial effects on eosinophil survival. Thus, SIRPα/CD172a is a potential therapeutic target for eosinophil-associated diseases.

Original languageEnglish
Pages (from-to)2268-2277
Number of pages10
JournalJournal of Immunology
Volume187
Issue number5
DOIs
StatePublished - 1 Sep 2011

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