SIRPα/CD172a Regulates Eosinophil Homeostasis

The Journal of Immunology: Official Journal of the American Association of Immunologists

Yun-Jae Jung¹  Ju-Young Seoh¹  Mikako Yamasaki¹  Eiji Umemoto¹  Katsuyuki Aozasa¹  Takashi Matozaki¹  Masaaki Murakami⁴  Masayuki Miyasaka⁷  Erina Hata⁷  So-Youn Woo⁷  Noel Verjan Garcia⁸  Myoung Ho Jang⁸  Yasuyuki Saito⁸ 

[1]Department of Microbiology, Graduate School of Medicine, Ewha Womans University, Seoul 120-750, Korea

[2]Department of Microbiology, Graduate School of Medicine, Gachon University of Medicine and Science, Incheon 405-835, South Korea

[3]Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512, Japan

[4]Laboratory of Developmental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan

[5]Laboratory of Gastrointestinal Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan

[6]Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan

[7]Laboratory of Immunodynamics, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan

DOI  :  10.4049/jimmunol.1101008

学科分类：生物科学（综合）

来源: American Association of Immunologists

【 摘 要 】

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 SIRPα 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.

【 授权许可】

CC BY