研究人员发现了可抑制肉芽肿性炎症反应的信号通路，该研究或可为自身免疫性疾病的治疗提供新思路，其相关论文近日发表在《科学-信号转导》（Science Signaling）杂志上。
肉芽肿的形成是机体抗细胞内细菌的一个重要机制，但过度的肉芽肿性炎症反应会对机体造成负面影响。
辅助性T细胞17（TH17）在包括肉芽肿在内的自身免疫和炎症性疾病发生过程中具有重要作用。
研究者发现，信号转导子和转录激活子3（STAT3）在CD4+T细胞向TH17细胞的分化过程中起重要作用，PDZ-LIM域蛋白PDLIM2作为核泛素E3连接酶抑制STAT3的作用，进而抑制TH17细胞的活化聚集和肉芽肿的形成。
PDLIM2促使STAT3聚泛素化和蛋白酶体降解，从而破坏STAT3介导基因的活化。
此外，细胞内若缺乏PDLIM2，则会导致STAT3在核内堆积，促使TH17细胞分化，进而促进肉芽肿形成。
该研究表明，PDLIM2在抑制TH17细胞介导的炎症反应过程中具有重要作用，它通过抑制STAT3信号发挥作用，为自身免疫性疾病提供了治疗靶点。（生物谷bioon.com）
doi:10.1126/scisignal.2001637
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PDLIM2 Inhibits T Helper 17 Cell Development and Granulomatous Inflammation Through Degradation of STAT3
Takashi Tanaka, Yu Yamamoto, Ryuta Muromoto, Osamu Ikeda, Yuichi Sekine, Michael J. Grusby, Tsuneyasu Kaisho, and Tadashi Matsuda.
Granuloma formation is an important host defense mechanism against intracellular bacteria; however, uncontrolled granulomatous inflammation is pathologic. T helper 17 (TH17) cells are thought to have a pathogenic role in autoimmune and inflammatory diseases, including in granulomas. Here, we report that the PDZ-LIM domain protein PDLIM2 inhibited TH17 cell development and granulomatous responses by acting as a nuclear ubiquitin E3 ligase that targeted signal transducer and activator of transcription 3 (STAT3), a transcription factor critical for the commitment of na?ve CD4+ T cells to the TH17 lineage. PDLIM2 promoted the polyubiquitination and proteasomal degradation of STAT3, thereby disrupting STAT3-mediated gene activation. Deficiency in PDLIM2 resulted in the accumulation of STAT3 in the nucleus, enhanced the extent of TH17 cell differentiation, and exacerbated granuloma formation. This study delineates an essential role for PDLIM2 in inhibiting TH17 cell-mediated inflammatory responses by suppressing STAT3 signaling and provides a potential therapeutic target for the treatment of autoimmune diseases.
