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SIRPα/CD172α regulates eosinophil homeostasis
- SIRPα/CD172α regulates eosinophil homeostasis
- Garcia N.V.; Umemoto E.; Saito Y.; Yamasaki M.; Hata E.; Matozaki T.; Murakami M.; Jung Y.-J.; Woo S.-Y.; Seoh J.-Y.; Jang M.H.; Aozasa K.; Miyasaka M.
- Ewha Authors
- 서주영; 우소연
- SCOPUS Author ID
- 서주영; 우소연
- Issue Date
- Journal Title
- Journal of Immunology
- vol. 187, no. 5, pp. 2268 - 2277
- SCI; SCIE; SCOPUS
- 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. Copyright © 2011 by The American Association of Immunologists, Inc.
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