The role of mTORC2/RICTOR in immune cells and inflammatory diseases.

IF 6.2 3区医学 Q2 CELL BIOLOGY

Inflammation Research Pub Date : 2026-09-17 DOI:10.1007/s00011-026-02365-9

Jingting Xu, Wenxin Zhong, Fei Xin, Fei Xu, Zehang Zheng, Fengjing Guo

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Abstract

Background: mTORC2, defined by its core component RICTOR, is a key regulator of immune cell function and inflammation, yet its roles have long been underappreciated due to lack of specific inhibitors and in vivo tools.

Objective: This review summarizes the current understanding of mTORC2-specific signaling (via AKT, SGK1, and PKC) in regulating the development, differentiation, and effector functions of diverse immune cells, and discusses its emerging roles in immune cell inflammation and tissue-specific inflammation.

Method: We synthesized findings from recent studies using conditional knockout mouse models, pharmacological inhibitors, and clinical samples.

Conclusion: mTORC2 controls Th1/Th2 differentiation, Treg stability, and memory T cell formation; regulates BCR signaling and plasma cell survival; and modulates macrophage M2 polarization, DC maturation, and NK cell function. In tissue inflammation, mTORC2 plays context-dependent roles-exacerbating osteoarthritis and pancreatitis but restraining pro-inflammatory polarization in colorectal cancer. Dual mTORC1/2 inhibitors (e.g., AZD2014) have shown early promise, though challenges remain regarding efficacy, toxicity, and immunomodulatory complexity.

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mTORC2/RICTOR在免疫细胞和炎症性疾病中的作用

背景：mTORC2由其核心成分RICTOR定义，是免疫细胞功能和炎症的关键调节因子，但由于缺乏特异性抑制剂和体内工具，其作用长期未被充分认识。目的：本文综述了目前对mtorc2特异性信号（通过AKT、SGK1和PKC）调控多种免疫细胞的发育、分化和效应功能的认识，并讨论了其在免疫细胞炎症和组织特异性炎症中的新作用。方法：我们综合了最近使用条件敲除小鼠模型、药物抑制剂和临床样本的研究结果。结论：mTORC2控制Th1/Th2分化、Treg稳定性和记忆T细胞形成；调控BCR信号和浆细胞存活；调节巨噬细胞M2极化、DC成熟和NK细胞功能。在组织炎症中，mTORC2发挥上下文依赖的作用——加剧骨关节炎和胰腺炎，但抑制结肠直肠癌的促炎极化。双重mTORC1/2抑制剂（例如AZD2014）已经显示出早期的前景，尽管在疗效、毒性和免疫调节复杂性方面仍然存在挑战。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammation Research 医学-免疫学

CiteScore

9.90

自引率

1.50%

发文量

134

审稿时长

3-8 weeks

期刊介绍： Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.