Retinoic acid and TGF-β orchestrate organ-specific programs of tissue residency

被引：4

作者：

Obers, Andreas ^{[1
]}

Poch, Tobias ^{[1
]}

Rodrigues, Grace ^{[2
]}

Christo, Susan N. ^{[1
]}

Gandolfo, Luke C. ^{[1
,3
,4
]}

Fonseca, Raissa ^{[1
]}

Zaid, Ali ^{[1
]}

Kuai, Joey En Yu ^{[1
]}

Lai, Hongjin ^{[1
,5
,6
]}

Zareie, Pirooz ^{[1
]}

Yakou, Marina H. ^{[7
]}

Dryburgh, Lachlan ^{[1
]}

Burn, Thomas N. ^{[1
]}

Dosser, James ^{[1
]}

Buquicchio, Frank A. ^{[8
,9
]}

Lareau, Caleb A. ^{[8
,9
]}

Walsh, Calum ^{[1
]}

Judd, Louise ^{[1
]}

Theodorou, Maria Rafailia ^{[10
]}

Gutbrod, Katharina ^{[11
]}

Doermann, Peter ^{[11
]}

Kingham, Jenny ^{[12
,13
]}

Stinear, Tim ^{[1
]}

Kallies, Axel ^{[1
]}

Schroeder, Jan ^{[1
]}

Mueller, Scott N. ^{[1
]}

Park, Simone L. ^{[1
,14
,15
]}

Speed, Terence P. ^{[3
,4
]}

Satpathy, Ansuman T. ^{[8
,9
,16
,17
]}

Phan, Tri Giang ^{[18
,19
]}

Wilhelm, Christoph ^{[10
]}

Zaph, Colby ^{[2
]}

Evrard, Maximilien ^{[1
]}

Mackay, Laura K. ^{[1
]}

机构：

[1] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia

[2] Monash Univ, Biomed Discovery Inst, Dept Biochem & Mol Biol, Clayton, Vic, Australia

[3] Univ Melbourne, Sch Math & Stat, Melbourne, Vic, Australia

[4] Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia

[5] Sichuan Univ, West China Hosp, Dept Thorac Surg, Chengdu, Peoples R China

[6] Sichuan Univ, West China Hosp, Inst Thorac Oncol, Chengdu, Peoples R China

[7] La Trobe Univ, Sch Canc Med, Olivia Newton John Canc Res Inst, Heidelberg, Vic, Australia

[8] Stanford Univ, Dept Pathol, Stanford, CA USA

[9] Stanford Univ, Program Immunol, Stanford, CA USA

[10] Univ Bonn, Inst Clin Chem & Clin Pharmacol, Immunopathol Unit, Bonn, Germany

[11] Univ Bonn, Inst Mol Physiol & Biotechnol Plants, Bonn, Germany

[12] Australian BioResources Pty Ltd, Moss Vale, NSW, Australia

[13] Garvan Inst Med Res, Anim Serv, Sydney, NSW, Australia

[14] Univ Penn, Perelman Sch Med, Inst Immunol & Immune Hlth, Philadelphia, PA USA

[15] Univ Penn, Perelman Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA USA

[16] Stanford Univ, Parker Inst Canc Immunotherapy, Stanford, CA USA

[17] Gladstone UCSF Inst Genom Immunol, San Francisco, CA USA

[18] Garvan Inst Med Res, Precis Immunol Program, Sydney, NSW, Australia

[19] UNSW Sydney, Fac Med & Hlth, Sch Clin Med, St Vincents Healthcare Clin Campus, Sydney, NSW, Australia

来源：

IMMUNITY | 2024年 / 57卷 / 11期

基金：

澳大利亚国家健康与医学研究理事会;

关键词：

MEMORY T-CELLS; DENDRITIC CELLS; IMMUNE-SYSTEM; VITAMIN-A; EFFECTOR; INFECTION; DIFFERENTIATION; MAINTENANCE; EXPRESSION; SPECIALIZATION;

D O I：

10.1016/j.immuni.2024.09.015

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Tissue-resident memory T (TRM) cells are integral to tissue immunity, persisting in diverse anatomical sites where they adhere to a common transcriptional framework. How these cells integrate distinct local cues to adopt the common TRM cell fate remains poorly understood. Here, we show that whereas skin TRM cells strictly require transforming growth factor b (TGF- beta) for tissue residency, those in other locations utilize the metabolite retinoic acid (RA) to drive an alternative differentiation pathway, directing a TGF-beta-independent tissue residency program in the liver and synergizing with TGF-beta to drive TRM cells in the small intestine. We found that RA was required for the long-term maintenance of intestinal TRM populations, in part by impeding their retrograde migration. Moreover, enhanced RA signaling modulated TRM cell phenotype and function, a phenomenon mirrored in mice with increased microbial diversity. Together, our findings reveal RA as a fundamental component of the host-environment interaction that directs immunosurveillance in tissues.

引用

页码：2615 / +

页数：29

共 93 条

[1] Critical Role for All-trans Retinoic Acid for Optimal Effector and Effector Memory CD8 T Cell Differentiation [J].