| First Author | Ben Baruch-Morgenstern N | Year | 2014 |
| Journal | Nat Immunol | Volume | 15 |
| Issue | 1 | Pages | 36-44 |
| PubMed ID | 24212998 | Mgi Jnum | J:208993 |
| Mgi Id | MGI:5565531 | Doi | 10.1038/ni.2757 |
| Citation | Ben Baruch-Morgenstern N, et al. (2014) Paired immunoglobulin-like receptor A is an intrinsic, self-limiting suppressor of IL-5-induced eosinophil development. Nat Immunol 15(1):36-44 |
| abstractText | 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 beta(2)-microglobulin (beta(2)M) 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. |
