SHIP-1 differentially regulates IgE-induced IL-10 and antiviral responses in human monocytes.
SHIP-1 differentially regulates IgE-induced IL-10 and antiviral responses in human monocytes.
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SHIP-1 差异性调节人单核细胞中 IgE 诱导的 IL-10 和抗病毒反应。
DOI：
10.1101/2024.02.07.579109
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Rowe,ReginaK
中科院分区：
文献类型：
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作者：
Solleti,SivaKumar;Matthews,BaileyE;Rowe,ReginaK
IgE介导的单核细胞刺激调节多种细胞功能，包括细胞成熟、细胞因子释放、抗病毒反应和T细胞分化。高亲和力IgE受体FcεRI的表达与血清IgE水平和特应性疾病密切相关。在肥大细胞和嗜碱性粒细胞中，调节FcεRI效应器功能的信号分子已得到充分研究;然而，对单核细胞中的信号和调节机制知之甚少。本研究旨在鉴定人单核细胞中IgE介导的细胞因子释放的调节剂。SHIP-1被鉴定为IgE诱导的IL-10产生的负调节剂。还确定了IgE介导的刺激和SHIP-1抑制降低了脂质体poly（I：C）刺激后的抗病毒IP-10产生，表明SHIP-1在IgE驱动和抗病毒反应途径中的差异调节。IgE介导的单核细胞刺激后，SHIP-1和NF-κB被激活，NF-κB激活与SHIP-1和FcεRIα细胞表达水平相关。据我们所知，这是第一项确定SHIP-1在调节人单核细胞中IgE介导的抗病毒反应中的作用的研究。鉴于单核细胞在炎症和免疫反应中的重要性，更好地理解FcεRI受体下游的信号传导和调节机制可能会导致过敏性疾病的新治疗靶点。
IgE‐mediated stimulation of monocytes regulates multiple cellular functions including cellular maturation, cytokine release, antiviral responses, and T‐cell differentiation. Expression of the high‐affinity IgE receptor, FcεRI, is closely linked to serum IgE levels and atopic disease. The signaling molecules regulating FcεRI effector functions have been well studied in mast cells and basophils; however, less is known about the signaling and regulatory mechanisms in monocytes. This study sought to identify regulators of IgE‐mediated cytokine release in human monocytes. SHIP‐1 was identified as a negative regulator of IgE‐induced IL‐10 production. It was also determined that IgE‐mediated stimulation and SHIP‐1 inhibition decreased antiviral IP‐10 production after liposomal poly(I:C) stimulation, indicating differential regulation by SHIP‐1 in IgE‐driven and antiviral response pathways. SHIP‐1 and NF‐κB were activated following IgE‐mediated stimulation of monocytes, and NF‐κB activation was related to both SHIP‐1 and FcεRIα cellular expression levels. To our knowledge, this is the first study to identify a role for SHIP‐1 in regulating IgE‐mediated and antiviral responses in human monocytes. Given the importance of monocytes in inflammation and immune responses, a better understanding of the signaling and regulatory mechanisms downstream of the FcεRI receptor could lead to new therapeutic targets in allergic disease.