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- Title
Paired immunoglobulin-like receptor A is an intrinsic, self-limiting suppressor of IL-5-induced eosinophil development.
- Authors
Baruch-Morgenstern, Netali Ben; Shik, Dana; Moshkovits, Itay; Itan, Michal; Karo-Atar, Danielle; Bouffi, Carine; Fulkerson, Patricia C; Rashkovan, Diana; Jung, Steffen; Rothenberg, Marc E; Munitz, Ariel
- Abstract
Eosinophilia is a hallmark characteristic of T helper type 2 (TH2) 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.
- Subjects
IMMUNOGLOBULIN receptors; INTERLEUKIN-5; EOSINOPHIL disorders; T helper cells; GROWTH factors; BONE marrow; MICROGLOBULINS
- Publication
Nature Immunology, 2014, Vol 15, Issue 1, p36
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2757