@article{5a111309924940c2bdc8b40cd8d2b29e,
title = "Paired immunoglobulin-like receptor A is an intrinsic, self-limiting suppressor of IL-5-induced eosinophil development",
abstract = "Eosinophilia is a hallmark characteristic of T helper type 2 (T H2) cell-associated diseases and is critically regulated by the central eosinophil growth factor interleukin 5 (IL-5). Here we demonstrate that IL-5 activity in eosinophils was regulated by paired immunoglobulin-like receptors PIR-A and PIR-B. Upon self-recognition of β2- microglobulin (β2M) molecules, PIR-B served as a permissive checkpoint for IL-5-induced development of eosinophils by suppressing the proapoptotic activities of PIR-A, which were mediated by the Grb2-Erk-Bim pathway. PIR-B-deficient bone marrow eosinophils underwent compartmentalized apoptosis, resulting in decreased blood eosinophilia in naive mice and in mice challenged with IL-5. Subsequently, Pirb-/- mice displayed impaired aeroallergen-induced lung eosinophilia and induction of lung TH2 cell responses. Collectively, these data uncover an intrinsic, self-limiting pathway regulating IL-5-induced expansion of eosinophils, which has broad implications for eosinophil-associated diseases.",
author = "Baruch-Morgenstern, {Netali Ben} and Dana Shik and Itay Moshkovits and Michal Itan and Danielle Karo-Atar and Carine Bouffi and Fulkerson, {Patricia C.} and Diana Rashkovan and Steffen Jung and Rothenberg, {Marc E.} and Ariel Munitz",
note = "Marie-Curie Reintegration [256311]; Israel Science Foundation [955/11, 1708/11]; Israel Cancer Research Foundation Research Career Development Award; Fritz Thyssen Foundation; US-Israel Bi-national Science Foundation [2009222]; US National Institutes of Health NIAID [R01AI083450, R37AI045898]; Campaign Urging Research for Eisonophilic Disease (CURED) Foundation; Buckeye FoundationWe thank H. Kubagawa (University of Alabama) for providing Pirb<SUP>-/-</SUP> mice, and S.P. Hogan, O. Mandelboim, I. Bachelet, N. Osherov and A. Ben-Baruch for critically reviewing this manuscript and helpful discussions. This work was performed in partial fulfillment of the requirements for the PhD degree of N.B.B.-M., and D.S. at Tel Aviv University. Supported by the FP7 Marie-Curie Reintegration grant (256311), the Israel Science Foundation (955/11 and 1708/11) the Israel Cancer Research Foundation Research Career Development Award and the Fritz Thyssen Foundation (to A.M.); the US-Israel Bi-national Science Foundation (2009222 to A.M. and M.E.R.); US National Institutes of Health NIAID (R01AI083450 and R37AI045898), Campaign Urging Research for Eisonophilic Disease (CURED) Foundation and Buckeye Foundation (to M.E.R.).",
year = "2014",
month = jan,
day = "1",
doi = "https://doi.org/10.1038/ni.2757",
language = "American English",
volume = "15",
pages = "36--44",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Research",
number = "1",
}