Paired immunoglobulin-like receptor A is an intrinsic, self-limiting suppressor of IL-5-induced eosinophil development.
Paired immunoglobulin-like receptor A is an intrinsic, self-limiting suppressor of IL-5-induced eosinophil development.
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DOI：
10.1038/ni.2757
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发表时间：
2014-01
影响因子：
30.5
通讯作者：
Munitz, Ariel
中科院分区：
文献类型：
--
作者：
Ben Baruch-Morgenstern, Netali;Shik, Dana;Moshkovits, Itay;Itan, Michal;Karo-Atar, Danielle;Bouffi, Carine;Fulkerson, Patricia C.;Rashkovan, Diana;Jung, Steffen;Rothenberg, Marc E.;Munitz, Ariel
嗜酸性粒细胞增多症是th2相关疾病的标志性特征，受中央嗜酸性粒细胞生长因子白介素5 （IL-5）的关键调控。本研究表明，IL-5在嗜酸性粒细胞中的活性受到配对免疫球蛋白样受体(PIR)-A和PIR- b的调节。在自我识别β2M分子后，PIR-B通过抑制Grb2-Erk-Bim途径介导的PIR-A促凋亡活性，作为il -5诱导的嗜酸性粒细胞发育的许可检查点。pir - b缺陷骨髓（BM）嗜酸性粒细胞发生区隔性凋亡，导致naïve、IL-5和空气过敏原挑战小鼠血嗜酸性粒细胞减少。随后，Pirb - / -小鼠表现出空气过敏原诱导的肺嗜酸性粒细胞受损和肺TH2反应的诱导。总的来说，这些数据揭示了调节il- 5诱导的嗜酸性粒细胞扩张的内在的、自我限制的途径，这对嗜酸性粒细胞相关疾病具有广泛的意义。
Eosinophilia is a hallmark characteristic of TH2-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 receptor (PIR)-A and PIR-B. Upon self-recognition of β2M molecules, PIR-B served as a permissive checkpoint for IL-5-induced eosinophil development by suppressing the pro-apoptotic activities of PIR-A, which were mediated by the Grb2-Erk-Bim pathway. PIR-B-deficient bone marrow (BM) eosinophils underwent compartmentalized apoptosis, resulting in decreased blood eosinophilia in naïve, IL-5- and aeroallergen-challenged mice. Subsequently, Pirb−/− mice displayed impaired aeroallergen-induced lung eosinophilia and induction of lung TH2 responses. Collectively, these data uncovers an intrinsic, self-limiting pathway regulating IL-5-induced eosinophil expansion, which has broad implications for eosinophil-associated diseases.
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DOI：
10.1038/nri3341
发表时间：
2013-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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配对的免疫球蛋白样受体PIR-A和PIR-B的生化性质和细胞分布。
影响因子：
15.3
作者：
Kubagawa, H;Chen, C C;Ho, L H;Shimada, T S;Gartland, L;Mashburn, C;Uehara, T;Ravetch, J V;Cooper, M D
通讯作者：
Cooper, M D
影响因子：
32.4
作者：
Kopf, M;Brombacher, F;Matthaei, KI
通讯作者：
Matthaei, KI
影响因子：
20.3
作者：
Munitz, A;Bachelet, I;Levi-Schaffer, F
通讯作者：
Levi-Schaffer, F
IL-5 与趋化因子嗜酸细胞趋化因子协同作用，诱导体内嗜酸性粒细胞积聚。
影响因子：
15.3
作者：
Collins, P. D.;Marleau, S.;Griffiths-Johnson, D. A.;Jose, P. J.;Williams, T. J.
通讯作者：
Williams, T. J.