Common γ-Chain-Dependent Signals Confer Selective Survival of Eosinophils in the Murine Small Intestine

Abstract

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 γ-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 γ-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 γ-chain-dependent signals might profoundly affect eosinophil function and homeostasis.

Immunity to gastrointestinal nematode infections

“…As with IL-13, it is secreted mainly by ILC2, but functions predominantly as an eosinophil recruitment and growth factor. [79][80][81] Eosinophils, which make up only a fraction of circulating leukocytes, are relatively abundant in the intestinal tract 82 and have traditionally been associated with combating parasites. There are little data, however, to suggest that deficiency in either IL-5 or eosinophils affects the polarization of protective immunity or by extension the outcome of infection, despite that eosinophil-derived mediators can skew dendritic cells to promote type 2 immunity.…”

The puzzle of intestinal lamina propria dendritic cells and macrophages

“…Intestinal eosinophils, which in the intestine express CD11c [9], might serve as an instructive example. Microscopy detects only few eosinophils per villus and the number of eosinophils that can be isolated is similar to that predicted by microscopic analysis.…”

The Origin and Maturity of Dendritic Cells Determine the Pattern of Sphingosine 1-Phosphate Receptors Expressed and Required for Efficient Migration

“…Mice were sacrificed 12 h later, and DCs were isolated from the MLN. LP DCs were isolated as described by Carlens et al (30). The numbers of MLN and LP CD103 + migratory DCs were determined by flow cytometry.…”