TY - JOUR
T1 - Paired immunoglobulin-like receptor A is an intrinsic, self-limiting suppressor of IL-5-induced eosinophil development
AU - Baruch-Morgenstern, Netali Ben
AU - Shik, Dana
AU - Moshkovits, Itay
AU - Itan, Michal
AU - Karo-Atar, Danielle
AU - Bouffi, Carine
AU - Fulkerson, Patricia C.
AU - Rashkovan, Diana
AU - Jung, Steffen
AU - Rothenberg, Marc E.
AU - Munitz, Ariel
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84891018837&partnerID=8YFLogxK
U2 - 10.1038/ni.2757
DO - 10.1038/ni.2757
M3 - Article
AN - SCOPUS:84891018837
SN - 1529-2908
VL - 15
SP - 36
EP - 44
JO - Nature Immunology
JF - Nature Immunology
IS - 1
ER -
