Iron-dependent epigenetic modulation promotes pathogenic T cell differentiation in lupus

被引：53

作者：

Gao, Xiaofei ^{[1
,2
,3
,4
]}

Song, Yang ^{[1
,2
,3
,4
]}

Wu, Jiali ^{[1
,2
,3
,4
]}

Lu, Shuang ^{[1
,2
,3
,4
]}

Min, Xiaoli ^{[1
,2
,3
,4
]}

Liu, Limin ^{[1
,2
,3
,4
]}

Hu, Longyuan ^{[1
,2
,3
,4
]}

Zheng, Meiling ^{[1
,2
,3
,4
]}

Du, Pei ^{[1
,2
,3
,4
]}

Yu, Yaqin ^{[1
,2
,3
,4
]}

Long, Hai ^{[1
,2
,3
,4
]}

Wu, Haijing ^{[1
,2
,3
,4
]}

Jia, Sujie ^{[5
]}

Yu, Di ^{[6
]}

Lu, Qianjin ^{[1
,2
,3
,4
,7
]}

Zhao, Ming ^{[1
,2
,3
,4
]}

机构：

[1] Cent South Univ, Xiangya Hosp 2, Dept Dermatol, Hunan Key Lab Med Epigen, Changsha, Peoples R China

[2] Chinese Acad Med Sci, Res Unit Key Technol Diag & Treatment Immune Rela, Changsha, Peoples R China

[3] Clin Med Res Ctr Major Skin Dis & Skin Hlth Hunan, Changsha, Peoples R China

[4] Cent South Univ, Clin Immunol Res Ctr, Changsha, Peoples R China

[5] Cent South Univ, Xiangya Hosp 3, Dept Pharm, Changsha, Peoples R China

[6] Univ Queensland, Fac Med, Diamantina Inst, Brisbane, Qld, Australia

[7] Chinese Acad Med Sci & Peking Union Med Coll, Inst Dermatol, 12 Jiang Wangmiao St, Nanjing 210042, Peoples R China

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2022年 / 132卷 / 09期

基金：

中国国家自然科学基金;

关键词：

DNA METHYLATION; DISEASE-ACTIVITY; IMMUNE-RESPONSE; DOWN-REGULATION; HOMEOSTASIS; DEMETHYLATION; CONTRIBUTES; ACTIVATION; INDUCTION; FERRITIN;

D O I：

10.1172/JCI152345

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The trace element iron affects immune responses and vaccination, but knowledge of its role in autoimmune diseases is limited. Expansion of pathogenic T cells, especially T follicular helper (Tfh) cells, has great significance to systemic lupus erythematosus (SLE) pathogenesis. Here, we show an important role of iron in regulation of pathogenic T cell differentiation in SLE. We found that iron overload promoted Tfh cell expansion, proinflammatory cytokine secretion, and autoantibody production in lupus-prone mice. Mice treated with a high-iron diet exhibited an increased proportion of Tfh cell and antigencell differentiation. We demonstrated that the miR-21/BDH2 axis drove iron accumulation during Tfh cell differentiation and might be critical for eliminating pathogenic Th cells and might help improve the management of patients with SLE.

引用

页数：19

共 64 条

[1] PD-1hiCXCR5- T peripheral helper cells promote B cell responses in lupus via MAF and IL-21 [J].

Bocharnikov, Alexandra, V ;

Keegan, Joshua ;

Wacleche, Vanessa S. ;

Cao, Ye ;

Fonseka, Chamith Y. ;

Wang, Guoxing ;

Muise, Eric S. ;

Zhang, Kelvin X. ;

Arazi, Arnon ;

Keras, Gregory ;

Li, Zhihan J. ;

Qu, Yujie ;

Gurish, Michael F. ;

Petri, Michelle ;

Guyon, Jill P. ;

Putterman, Chaim ;

Wofsy, David ;

James, Judith A. ;

Guthridge, Joel M. ;

Diamond, Betty ;

Anolik, Jennifer H. ;

Mackey, Matthew F. ;

Alves, Stephen E. ;

Nigrovic, Peter A. ;

Costenbader, Karen H. ;

Brenner, Michael B. ;

Lederer, James A. ;

Rao, Deepak A. .

JCI INSIGHT, 2019, 4 (20)

[2] T Cell Abnormalities in the Pathogenesis of Systemic Lupus Erythematosus: an Update [J].

Chen, Ping-Min ;

Tsokos, George C. .

CURRENT RHEUMATOLOGY REPORTS, 2021, 23 (02)

[3] Circulating Follicular Helper-Like T Cells in Systemic Lupus Erythematosus [J].

Choi, Jin-Young ;

Ho, John Hsi-en ;

Pasoto, Sandra G. ;

Bunin, Viviane ;

Kim, Sang Taek ;

Carrasco, Solange ;

Borba, Eduardo F. ;

Goncalves, Celio R. ;

Costa, Priscila R. ;

Kallas, Esper G. ;

Bonfa, Eloisa ;

Craft, Joseph .

ARTHRITIS & RHEUMATOLOGY, 2015, 67 (04) :988-999

[4] Epigenetic Reprogramming in Naive CD4+T Cells Favoring T Cell Activation and Non-Th1 Effector T Cell Immune Response as an Early Event in Lupus Flares [J].

Coit, Patrick ;

Dozmorov, Mikhail G. ;

Merrill, Joan T. ;

McCune, W. Joseph ;

Maksimowicz-McKinnon, Kathleen ;

Wren, Jonathan D. ;

Sawalha, Amr H. .

ARTHRITIS & RHEUMATOLOGY, 2016, 68 (09) :2200-2209

[5] The Role of Iron Regulation in Immunometabolism and Immune-Related Disease [J].

Cronin, Shane J. F. ;

Woolf, Clifford J. ;

Weiss, Guenter ;

Penninger, Josef M. .

FRONTIERS IN MOLECULAR BIOSCIENCES, 2019, 6

[6] The metabolite BH4 controls T cell proliferation in autoimmunity and cancer [J].

Cronin, Shane J. F. ;

Seehus, Corey ;

Weidinger, Adelheid ;

Talbot, Sebastien ;

Reissig, Sonja ;

Seifert, Markus ;

Pierson, Yann ;

McNeill, Eileen ;

Longhi, Maria Serena ;

Turnes, Bruna Lenfers ;

Kreslavsky, Taras ;

Kogler, Melanie ;

Hoffmann, David ;

Ticevic, Melita ;

Scheffer, Debora da Luz ;

Tortola, Luigi ;

Cikes, Domagoj ;

Jais, Alexander ;

Rangachari, Manu ;

Rao, Shuan ;

Paolino, Magdalena ;

Novatchkova, Maria ;

Aichinger, Martin ;

Barrett, Lee ;

Latremoliere, Alban ;

Wirnsberger, Gerald ;

Lametschwandtner, Guenther ;

Busslinger, Meinrad ;

Zicha, Stephen ;

Latini, Alexandra ;

Robson, Simon C. ;

Waisman, Ari ;

Andrews, Nick ;

Costigan, Michael ;

Channon, Keith M. ;

Weiss, Guenter ;

Kozlov, Andrey V. ;

Tebbe, Mark ;

Johnsson, Kai ;

Woolf, Clifford J. ;

Penninger, Josef M. .

NATURE, 2018, 563 (7732) :564-+

[7] Therapeutic effects of artesunate on lupus-prone MRL/lpr mice are dependent on T follicular helper cell differentiation and activation of JAK2-STAT3 signaling pathway [J].

Dang, Wen-Zhen ;

Li, Hui ;

Jiang, Bing ;

Nandakumar, Kutty Selva ;

Liu, Kai-Fei ;

Liu, Li-Xin ;

Yu, Xiao-Chen ;

Tan, Hui-Jing ;

Zhou, Chun .

PHYTOMEDICINE, 2019, 62

[8] A Mammalian Siderophore Synthesized by an Enzyme with a Bacterial Homolog Involved in Enterobactin Production [J].

Devireddy, Laxminarayana R. ;

Hart, Daniel O. ;

Goetz, David H. ;

Green, Michael R. .

CELL, 2010, 141 (06) :1006-1017

[9] Chelation of intracellular iron with the antifungal agent ciclopirox olamine induces cell death in leukemia and myeloma cells [J].

Eberhard, Yanina ;

McDermott, Sean P. ;

Wang, Xiaoming ;

Gronda, Marcela ;

Venugopal, Amudha ;

Wood, Tabitha E. ;

Hurren, Rose ;

Datti, Alessandro ;

Batey, Robert A. ;

Wrana, Jeffrey ;

Antholine, William E. ;

Dick, John ;

Schimmer, Aaron D. .

BLOOD, 2009, 114 (14) :3064-3073

[10] Affinity Enhancement of Antibodies: How Low-Affinity Antibodies Produced Early in Immune Responses Are Followed by High-Affinity Antibodies Later and in Memory B-Cell Responses [J].

Eisen, Herman N. .

CANCER IMMUNOLOGY RESEARCH, 2014, 2 (05) :381-392

← 1 2 3 4 5 6 7 →