The ELISA was developed using biotinylated anti-L chain Ab and st

The ELISA was developed using biotinylated anti-L chain Ab and streptavidin HRP (Jackson ImmunoResearch) plus ABTS (Sigma Aldrich) as substrate. We acknowledge the help of Patricia Simms in the FACS Core Facility at Loyola University, Chicago. This work was

supported by the National Institute of Health Grants AI50260 and AI068390 to KLK. The authors declare no financial or commercial conflict of interest. “
“Herein, we provide evidence that during allergic inflammation, CCL25 induces the selec-tive migration of IL-17+ γδ T cells mediated by α4β7 integrin. Intrapleural injection of CCL25 into ovalbumin (OVA)-immunized C57BL/6 mice triggered the accumulation of γδ T lymphocytes expressing selleck kinase inhibitor CCR9 (CCL25 receptor) and α4β7 integrin

in the pleura, but failed to attract αβ T lymphocytes. CCL25 attracted CCR6+ γδ T cells producing IL-17 (but not IFN-γ or IL-4). OVA challenge triggered increased production of CCL25 followed by the accumulation of CCR9+, α4β7+, and CCR6+/IL-17+ γδ click here T cells into the pleural cavities of OVA-immunized mice, which was inhibited by the in vivo neutralization of CCL25. The in vivo blockade of α4β7 integrin also inhibited the migration of IL-17+ γδ T lymphocytes (but not of αβ T lymphocytes) into mouse pleura after OVA challenge, suggesting that the CCL25/α4β7 integrin pathway is selective for γδ T cells. In addition, α4β7 integrin blockade impaired the in vitro transmigration of γδ T cells across endothelium (which expresses α4β7 ligands VCAM-1 and MadCAM-1), which was induced by CCL25 and by cell-free pleural washes recovered from OVA-challenged mice. Our results reveal that during an allergic reaction, CCL25 drives IL-17+ γδ T-cell mobilization to inflamed tissue via α4β7 integrin and modulates IL-17 levels. Lymphocytes bearing the γδ T-cell receptor (TCR) comprise Phospholipase D1 a minor T-lymphocyte subset in blood and secondary lymphoid tissues and are preferentially localized in epithelial

and mucosal tissues [[1, 2]]. This unique subset of lymphocytes can provide rapid tissue-specific immune responses, without the requirement of antigen presentation or clonal expansion, and is able to produce a large repertory of Th1-, Th2-, and Th17-associated cytokines [[2-6]]. These characteristics make γδ T cells a crucial first line of defense during infection, tissue damage, or stress. γδ T cells have been shown to migrate into the airways during allergic inflammation highly controlled by a chemotactic gradient of chemokines produced in tissue [[5, 7-11]]. We have previously demonstrated that allergen-induced γδ T-cell accumulation is paralleled with a marked production of chemokines in the tissue, including CCL25/TECK [[11]]. CCL25 is mostly described as a homeostatic chemokine that plays a major role in T-cell development in the thymus and in intraepithelial lymphocytes (IELs) homing into small intestine mucosa [[12]].

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