Ma Yanmei, Hossen Md Munnaf, Huang Jennifer Jin, Yin Zhihua, Du Jing, Ye Zhizhong, Zeng Miaoyu, Huang Zhong
Rheumatology Research Institute, Shenzhen Futian Hospital for Rheumatic Diseases, Shenzhen, China.
Department of Immunology, Biological Therapy Institute, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Health Science Center, Shenzhen University, Shenzhen, China.
Front Immunol. 2025 Feb 27;16:1513069. doi: 10.3389/fimmu.2025.1513069. eCollection 2025.
Growth arrest and DNA damage-inducible 45 (GADD45) proteins are critical stress sensors rapidly induced in response to genotoxic/physiological stress and regulate many cellular functions. Even though the primary function of the proteins is to block the cell cycle, inhibit cell proliferation, promote cell apoptosis, and repair DNA damage to cope with the damage caused by internal and external stress on the body, evidence has shown that GADD45 also has the function to modulate innate and adaptive immunity and plays a broader role in inflammatory and autoimmune diseases. In this review, we focus on the immunomodulatory role of GADD45 in inflammatory and autoimmune diseases. First, we describe the regulatory factors that affect the expression of GADD45. Then, we introduce its immunoregulatory roles on immune cells and the critical signaling pathways mediated by GADD45. Finally, we discuss its immunomodulatory effects in various inflammatory and autoimmune diseases.
生长停滞与DNA损伤诱导蛋白45（GADD45）是关键的应激传感器，可在响应基因毒性/生理应激时迅速被诱导，并调节多种细胞功能。尽管这些蛋白的主要功能是阻断细胞周期、抑制细胞增殖、促进细胞凋亡以及修复DNA损伤，以应对体内外应激对身体造成的损害，但有证据表明，GADD45还具有调节先天性和适应性免疫的功能，并且在炎症和自身免疫性疾病中发挥更广泛的作用。在这篇综述中，我们聚焦于GADD45在炎症和自身免疫性疾病中的免疫调节作用。首先，我们描述影响GADD45表达的调节因子。然后，我们介绍其对免疫细胞的免疫调节作用以及GADD45介导的关键信号通路。最后，我们讨论其在各种炎症和自身免疫性疾病中的免疫调节作用。
