Interleukin-3-dependent potentiation of IgE responsiveness in mouse basophils
Interleukin-3-dependent potentiation of IgE responsiveness in mouse basophils
复制标题
小鼠嗜碱性粒细胞 IgE 反应性的白细胞介素 3 依赖性增强
DOI：
10.1111/gtc.13007
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发表时间：
2023
期刊：
影响因子：
2.1
通讯作者：
Hida S.
中科院分区：
文献类型：
--
作者：
Kitano T.;Togawa K.;Takemori J.;Motoki Y.;Kishida K.;Itoh S.;Takamoto M.;Taki S.;Hida S.
嗜碱性粒细胞响应各种刺激而产生白细胞介素 (IL)-4，并可能有助于针对各种感染和过敏原的 2 型免疫反应。我们发现，新鲜从小鼠中分离出来的静息嗜碱性粒细胞会响应 IL-3 而产生 IL-4，但不会响应高亲和力 Fc 受体 (FcεRI) 交联 (CL)，但两者都需要包含接头 Fc 受体 γ 链 (FcRγ) 的基于免疫受体酪氨酸的激活基序 (ITAM)，而在体外被 IL-3 激活的嗜碱性粒细胞会对 FcεRI CL 产生响应。在用旋毛虫感染或给予超抗原后，获得了对 FcεRI CL 的反应性。由于培养的嗜碱性粒细胞在 IL-3 饥饿后恢复到静止状态，表面 FcεRI 水平保持不变，因此这种获取是可逆的，可能反映了需要蛋白质合成的细胞内事件。有趣的是，在对其他刺激的反应中观察到了类似的激活相关获取，包括已知通过 DAP-12 发出信号的 CD200R3 CL 和过敏原蛋白酶木瓜蛋白酶。这种对 FcεRI CL 的反应性的获得被 Jak 抑制剂抑制。因此，IL-3 信号在 Jak 下游分叉，分为两条不同的途径，一条导致 IL-4 的产生，另一条使嗜碱性粒细胞能够对依赖于包含 ITAM 的接头 DAP12 和 FcRγ 的刺激做出反应，以产生 IL-4。
Basophils produce interleukins (IL)‐4 in response to various stimuli and may contribute to type 2 immune responses to various infections and allergens. We found that resting basophils freshly isolated from mice produce IL‐4 in response to IL‐3 but not to high‐affinity Fc receptor (FcεRI) cross‐linking (CL), yet both required the immunoreceptor tyrosine‐based activation motif (ITAM) containing adaptor Fc receptor γ‐chain (FcRγ), while basophils activated in vitro by IL‐3 become responsive to FcεRI CL. Acquisition of responsiveness to FcεRI CL occurred upon infection withTrichinella spiralisor administration of superantigen. Because cultured basophils return to a quiescent state upon starvation with IL‐3 with surface FcεRI levels unchanged, this acquisition is reversible and probably reflects intracellular events requiring protein synthesis. Interestingly, similar activation‐associated acquisition was observed for responsiveness to other stimuli, including CD200R3 CL, which is known to signal via DAP‐12, and the allergen protease papain. This acquisition of responsiveness to FcεRI CL was inhibited by Jak inhibitor. Thus, the IL‐3 signal bifurcates downstream of Jak, into two distinct pathway, one leading to IL‐4 production and the other to render basophils competent to respond to stimuli dependent on ITAM‐containing adaptors DAP12 and FcRγ for IL‐4 production.