Stigmasterol Restores the Balance of Treg/Th17 Cells by Activating the Butyrate-PPARγ Axis in Colitis

被引：103

作者：

Wen, Shuting ^{[1
]}

He, Long ^{[1
]}

Zhong, Zhuotai ^{[1
]}

Zhao, Runyuan ^{[1
]}

Weng, Senhui ^{[1
]}

Mi, Hong ^{[2
]}

Liu, Fengbin ^{[2
,3
,4
]}

机构：

[1] Guangzhou Univ Chinese Med, Clin Coll 1, Guangzhou, Peoples R China

[2] Guangzhou Univ Chinese Med, Dept Gastroenterol, Affiliated Hosp 1, Guangzhou, Peoples R China

[3] Guangzhou Univ, Affiliated Hosp 1, Baiyun Hosp, Guangzhou, Peoples R China

[4] Guangzhou Univ Chinese Med, Lingnan Med Res Ctr, Guangzhou, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷

基金：

中国国家自然科学基金;

关键词：

inflammatory bowel disease; stigmasterol; microbiota; butyrate; PPAR gamma; Treg; Th17; balance; METABOLIC CHECKPOINT; BETA-SITOSTEROL; TREG CELLS; T-CELLS; MICROBIOTA; INNATE; IMMUNE; DIFFERENTIATION; INFLAMMATION; BACTERIA;

D O I：

10.3389/fimmu.2021.741934

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with gut microbiota disequilibrium and regulatory T (Treg)/T helper 17 (Th17) immune imbalance. Stigmasterol, a plant-derived sterol, has shown anti-inflammatory effects. Our study aimed to identify the effects of stigmasterol on experimental colitis and the related mechanisms. Stigmasterol treatment restored the Treg/Th17 balance and altered the gut microbiota in a dextran sodium sulfate (DSS)-induced colitis model. Transplantation of the faecal microbiota of stigmasterol-treated mice significantly alleviated inflammation. Additionally, stigmasterol treatment enhanced the production of gut microbiota-derived short-chain fatty acids (SCFAs), particularly butyrate. Next, human naive CD4+ T cells sorted from IBD patients were cultured under Treg- or Th17-polarizing conditions; butyrate supplementation increased the differentiation of Tregs and decreased Th17 cell differentiation. Mechanistically, butyrate activated peroxisome proliferator-activated receptor gamma (PPAR gamma) and reprogrammed energy metabolism, thereby promoting Treg differentiation and inhibiting Th17 differentiation. Our results demonstrate that butyrate-mediated PPAR gamma activation restores the balance of Treg/Th17 cells, and this may be a possible mechanism, by which stigmasterol attenuates IBD.

引用

页数：17

共 76 条

[1] Stigmasterol Alleviates Cutaneous Allergic Responses in Rodents [J].

Antwi, Aaro O. ;

Obiri, David D. ;

Osafo, Newman ;

Essel, Leslie B. ;

Forkuo, Arnold D. ;

Atobiga, Clement .

BIOMED RESEARCH INTERNATIONAL, 2018, 2018

[2] Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation [J].

Arpaia, Nicholas ;

Campbell, Clarissa ;

Fan, Xiying ;

Dikiy, Stanislav ;

van der Veeken, Joris ;

deRoos, Paul ;

Liu, Hui ;

Cross, Justin R. ;

Pfeffer, Klaus ;

Coffer, Paul J. ;

Rudensky, Alexander Y. .

NATURE, 2013, 504 (7480) :451-+

[3] Anti-nociceptive effect of stigmasterol in mouse models of acute and chronic pain [J].

Bandero Walker, Cristiani Isabel ;

Oliveira, Sara Marchesan ;

Tonello, Raquel ;

Rossato, Mateus Fortes ;

Brum, Evelyne da Silva ;

Ferreira, Juliano ;

Trevisan, Gabriela .

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2017, 390 (11) :1163-1172

[4] Fatigue in IBD: epidemiology, pathophysiology and management [J].

Borren, Nienke Z. ;

van der Woude, C. Janneke ;

Ananthakrishnan, Ashwin N. .

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2019, 16 (04) :247-259

[5] Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice [J].

Britton, Graham J. ;

Contijoch, Eduardo J. ;

Mogno, Ilaria ;

Vennaro, Olivia H. ;

Llewellyn, Sean R. ;

Ng, Ruby ;

Li, Zhihua ;

Mortha, Arthur ;

Merad, Miriam ;

Das, Anuk ;

Gevers, Dirk ;

McGovern, Dermot P. B. ;

Singh, Namita ;

Braun, Jonathan ;

Jacobs, Jonathan P. ;

Clemente, Jose C. ;

Grinspan, Ari ;

Sands, Bruce E. ;

Colombel, Jean-Frederic ;

Dubinsky, Marla C. ;

Faith, Jeremiah J. .

IMMUNITY, 2019, 50 (01) :212-+

[6] Gut Microbiota Regulation of T Cells During Inflammation and Autoimmunity [J].

Brown, Eric M. ;

Kenny, Douglas J. ;

Xavier, Ramnik J. .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 37, 2019, 2019, 37 :599-624

[7] Indole-3-carbinol prevents colitis and associated microbial dysbiosis in an IL-22-dependent manner [J].

Busbee, Philip B. ;

Menzel, Lorenzo ;

Alrafas, Haider Rasheed ;

Dopkins, Nicholas ;

Becker, William ;

Miranda, Kathryn ;

Tang, Chaunbing ;

Chatterjee, Saurabh ;

Singh, Udai P. ;

Nagarkatti, Mitzi ;

Nagarkatti, Prakash S. .

JCI INSIGHT, 2020, 5 (01)

[8] Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion [J].

Byndloss, Mariana X. ;

Olsan, Erin E. ;

Rivera-Chavez, Fabian ;

Tiffany, Connor R. ;

Cevallos, Stephanie A. ;

Lokken, Kristen L. ;

Torres, Teresa P. ;

Byndloss, Austin J. ;

Faber, Franziska ;

Gao, Yandong ;

Litvak, Yael ;

Lopez, Christopher A. ;

Xu, Gege ;

Napoli, Eleonora ;

Giulivi, Cecilia ;

Tsolis, Renee M. ;

Revzin, Alexander ;

Lebrilla, Carlito B. ;

Baumler, Andreas J. .

SCIENCE, 2017, 357 (6351) :570-+

[9] Clostridium butyricum, a butyrate-producing probiotic, inhibits intestinal tumor development through modulating Wnt signaling and gut microbiota [J].

Chen, Danfeng ;

Jin, Duochen ;

Huang, Shumin ;

Wu, Jingyi ;

Xu, Mengque ;

Liu, Tianyu ;

Dong, Wenxiao ;

Liu, Xiang ;

Wang, Sinan ;

Zhong, Weilong ;

Liu, Yi ;

Jiang, Ruihuan ;

Piao, Meiyu ;

Wang, Bangmao ;

Cao, Hailong .

CANCER LETTERS, 2020, 469 :456-467

[10] Rising in the East [J].

Chi, Kelly Rae .

NATURE, 2016, 540 (7634) :S100-S102

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