Divergent molecular networks program functionally distinct CD8+ skin-resident memory T cells

被引：19

作者：

Park, Simone L. ^{[1
,9
]}

Christo, Susan N. ^{[1
]}

Wells, Alexandria C. ^{[2
]}

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

Zaid, Ali ^{[1
]}

Alexandre, Yannick O. ^{[1
]}

Burn, Thomas N. ^{[1
]}

Schroeder, Jan ^{[1
]}

Collins, Nicholas ^{[2
]}

Han, Seong-Ji ^{[2
]}

Guillaume, Stephane M. ^{[1
]}

Evrard, Maximilien ^{[1
]}

Castellucci, Clara ^{[1
]}

Davies, Brooke ^{[1
]}

Osman, Maleika ^{[1
]}

Obers, Andreas ^{[1
]}

McDonald, Keely M. ^{[1
]}

Wang, Huimeng ^{[1
]}

Mueller, Scott N. ^{[1
]}

Kannourakis, George ^{[5
,6
]}

Berzins, Stuart P. ^{[1
,5
,6
]}

Mielke, Lisa A. ^{[7
]}

Carbone, Francis R. ^{[1
]}

Kallies, Axel ^{[1
]}

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

Belkaid, Yasmine ^{[2
,8
]}

Mackay, Laura K. ^{[1
]}

机构：

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

[2] Natl Inst Allergy & Infect Dis NIAID, Natl Inst Hlth, Metaorganism Immun Sect, Lab Host Immun & Microbiome, Bethesda, MD USA

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

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

[5] Federat Univ Australia, Inst Innovat Sci & Sustainabil, Ballarat, Vic, Australia

[6] Fiona Elsey Canc Res Inst, Ballarat, Vic, Australia

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

[8] NIAID, NIH, NIAID Microbiome Program, Bethesda, MD USA

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

来源：

SCIENCE | 2023年 / 382卷 / 6674期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

TISSUE-RESIDENT; RM CELLS; EXPRESSION; IMMUNITY; BETA; PSORIASIS; INFECTION; INSTRUCT; PATHWAY; HOBIT;

D O I：

10.1126/science.adi8885

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Skin-resident CD8(+) T cells include distinct interferon-gamma-producing [tissue-resident memory T type 1 (T(RM)1)] and interleukin-17 (IL-17)-producing (T(RM)17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms to establish tissue residence is unknown. In this work, we show that T(RM)1 and T(RM)17 cells navigate divergent trajectories to acquire tissue residency in the skin. T(RM)1 cells depend on a T-bet-Hobit-IL-15 axis, whereas T(RM)17 cells develop independently of these factors. Instead, c-Maf commands a tissue-resident program in T(RM)17 cells parallel to that induced by Hobit in T(RM)1 cells, with an ICOS-c-Maf-IL-7 axis pivotal to T(RM)17 cell commitment. Accordingly, by targeting this pathway, skin T(RM)17 cells can be ablated without compromising their T(RM)1 counterparts. Thus, skin-resident T cells rely on distinct molecular circuitries, which can be exploited to strategically modulate local immunity.

引用

页码：1073 / 1079

页数：7

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