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-Chain-Dependent Signals Confer Selective Survival of Eosinophils in the Murine Small Intestine1

*Institute of Immunology and
Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; and
Department of Immunology and Cell Biology, Research Center Borstel, Germany
Eosinophils are potent effector cells that are recruited to sites of inflammation. However, in some tissues, in particular in the gastrointestinal tract, eosinophils constitute an abundant leukocyte population also under homeostatic conditions. The lack of suitable isolation protocols restricted the analysis of these cells to histological assessment of cell numbers while important aspects of their phenotype, turnover, and functions remain unresolved. In this study, we report a protocol that allows the quantitative isolation of intestinal eosinophils. We characterized small intestinal eosinophils by flow cytometry as SSChighCD11b+CD11c+CCR3+Siglec-F+ cells. Intestinal eosinophils resembled eosinophils isolated from thymus and uterus but differed from eosinophils isolated from lung or blood. Eosinophils in intestine, thymus, and uterus showed in vivo a markedly higher life time compared with eosinophils present in lung and blood measured by incorporation of BrdU. This indicates that under steady-state conditions homeostasis of eosinophils is controlled by regulation of cell survival. Intestinal eosinophils are severely reduced in the intestines of Rag-2/common
-chain double-deficient mice but not Rag-2-deficient mice, correlating with differential expression of GM-CSF and CCL11 in both mouse strains. Moreover, under steady-state conditions, intestinal eosinophils constitutively express high levels of the common
-chain transcripts compared with lung eosinophils as well as eosinophils present under inflammatory conditions. These observations reveal a hitherto unrecognized diversity in phenotypic and functional properties of eosinophils and suggest that tissue-specific common
-chain-dependent signals might profoundly affect eosinophil function and homeostasis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by Deutsche Forschungsgemeinschaft Grants SFB621-A11 (to O.P.) and SFP566 (to R.F. and O.P.).
2 J.C. and B.W. contributed equally to this work and are named in alphabetical order.
3 Address correspondence and reprint requests to Dr. Oliver Pabst, Institute of Immunology, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. E-mail address: Pabst.Oliver{at}MH-Hannover.de
4 Abbreviations used in this paper:
c, common
chain; MHCII, MHC class II; LPC, lamina propria cell.
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