Paired immunoglobulin-like receptor A is an intrinsic, self-limiting suppressor of IL-5-induced eosinophil development

Netali Ben Baruch-Morgenstern, Dana Shik, Itay Moshkovits, Michal Itan, Danielle Karo-Atar, Carine Bouffi, Patricia C. Fulkerson, Diana Rashkovan, Steffen Jung, Marc E. Rothenberg, Ariel Munitz

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)36-44
Number of pages9
JournalNature Immunology
Volume15
Issue number1
DOIs
StatePublished - Jan 2014

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