文献类型： 外文期刊

作者： Poddar, Subhajit ¹ ; Chauvin, Samuel D. ¹ ; Archer, Christopher H. ² ; Qian, Wei ³ ; Castillo-Badillo, Jean A. ² ; Yin, Xin ⁴ ; Disbennett, W. Miguel ¹ ; Miner, Cathrine A. ¹ ; Holley, Joe A. ¹ ; V. Naismith, Teresa ¹ ; Stinson, W. Alexander ³ ; Wei, Xiaochao ³ ; Ning, Yue ¹ ; Fu, Jiayuan ¹ ; Ochoa, Trini A. ¹ ; Surve, Nehalee ¹ ; Zaver, Shivam A. ¹ ; Wodzanowski, Kimberly A. ⁶ ; Balka, Katherine R. ⁷ ; Venkatraman, Rajan ⁷ ; Liu, Canyu ¹ ; Rome, Kelly ⁸ ; Bailis, Will ⁸ ; Shiba, Yoko ⁹ ; Cherry, Sara ¹⁰ ; Shin, Sunny ⁶ ; Semenkovich, Clay F. ³ ; De Nardo, Dominic ⁷ ; Yoh, Sunnie ⁴ ; Roberson, Elisha D. O. ³ ; Chanda, Sumit K. ⁴ ; Kast, David J. ² ; Miner, Jonathan J. ¹ ;

作者机构： 1.Univ Penn, Perelman Sch Med, Div Rheumatol, Dept Med, Philadelphia, PA 19104 USA

2.Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA

3.Washington Univ, Sch Med, Dept Med, St. Louis, MO 63110 USA

4.Sanford Burnham Prebys Med Discovery Inst, Immun & Pathogenesis Program, La Jolla, CA 92037 USA

5.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin 150069, Peoples R China

6.Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

7.Monash Univ, Biomed Discovery Inst, Immun Program, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

8.Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA USA

9.Iwate Univ, Fac Sci & Engn, Morioka 0208551, Japan

10.Univ Penn, Perelman Sch Med, Inst Immunol & Immune Hlth, Philadelphia, PA 19104 USA

11.Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

12.Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

13.Univ Penn, Colton Ctr Autoimmun, Perelman Sch Med, Philadelphia, PA 19104 USA

期刊名称：CELL （ 影响因子：42.5； 五年影响因子：48.9 ）

ISSN： 0092-8674

年卷期： 2025 年 188 卷 6 期

页码：

收录情况： SCI

摘要： Stimulator of interferon genes (STING) transmits signals downstream of the cytosolic DNA sensor cyclic guanosine monophosphate-AMP synthase (cGAS), leading to transcriptional upregulation of cytokines. However, components of the STING signaling pathway, such as IRF3 and IFNAR1, are not essential for autoinflammatory disease in STING gain-of-function (STING-associated vasculopathy with onset in infancy [SAVI]) mice. Recent discoveries revealed that STING also functions as a proton channel that deacidifies the Golgi apparatus. Because pH impacts Golgi enzyme activity, protein maturation, and trafficking, we hypothesized that STING proton channel activity influences multiple Golgi functions. Here, we show that STING-mediated proton efflux non-transcriptionally regulates Golgi trafficking of protein cargos. This process requires the Golgi-associated protein ArfGAP2, a cell-type-specific dual regulator of STING-mediated proton efflux and signaling. Deletion of ArfGAP2 in hematopoietic and endothelial cells markedly reduces STING-mediated cytokine and chemokine secretion, immune cell activation, and autoinflammatory pathology in SAVI mice. Thus, ArfGAP2 facilitates STING-mediated signaling and cytokine release in hematopoietic cells, significantly contributing to autoinflammatory disease pathogenesis.