A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage

Hui-Fern Koay, Nicholas A Gherardin, Anselm Enders, Liyen Loh, Laura K Mackay, Catarina F Almeida, Brendan E Russ, Claudia A Nold-Petry, Marcel F Nold, Sammy Bedoui, Zhenjun Chen, Alexandra J Corbett, Sidonia B G Eckle, Bronwyn Meehan, Yves d'Udekem, Igor E Konstantinov, Martha Lappas, Ligong Liu, Chris C Goodnow, David P Fairlie & 9 others Jamie Rossjohn, Mark M Chong, Katherine Kedzierska, Stuart P Berzins, Gabrielle T Belz, James McCluskey, Adam P Uldrich, Dale I Godfrey, Daniel G Pellicci

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.

Original languageEnglish
Pages (from-to)1300-1311
Number of pages12
JournalNature Immunology
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2016

Keywords

  • innate immune cells
  • mucosal immunology

Cite this

Koay, H-F., Gherardin, N. A., Enders, A., Loh, L., Mackay, L. K., Almeida, C. F., ... Pellicci, D. G. (2016). A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. Nature Immunology, 17(11), 1300-1311. https://doi.org/10.1038/ni.3565
Koay, Hui-Fern ; Gherardin, Nicholas A ; Enders, Anselm ; Loh, Liyen ; Mackay, Laura K ; Almeida, Catarina F ; Russ, Brendan E ; Nold-Petry, Claudia A ; Nold, Marcel F ; Bedoui, Sammy ; Chen, Zhenjun ; Corbett, Alexandra J ; Eckle, Sidonia B G ; Meehan, Bronwyn ; d'Udekem, Yves ; Konstantinov, Igor E ; Lappas, Martha ; Liu, Ligong ; Goodnow, Chris C ; Fairlie, David P ; Rossjohn, Jamie ; Chong, Mark M ; Kedzierska, Katherine ; Berzins, Stuart P ; Belz, Gabrielle T ; McCluskey, James ; Uldrich, Adam P ; Godfrey, Dale I ; Pellicci, Daniel G. / A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. In: Nature Immunology. 2016 ; Vol. 17, No. 11. pp. 1300-1311.
@article{fe078a6953f142a8a170c231c88b7e9c,
title = "A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage",
abstract = "Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.",
keywords = "innate immune cells, mucosal immunology",
author = "Hui-Fern Koay and Gherardin, {Nicholas A} and Anselm Enders and Liyen Loh and Mackay, {Laura K} and Almeida, {Catarina F} and Russ, {Brendan E} and Nold-Petry, {Claudia A} and Nold, {Marcel F} and Sammy Bedoui and Zhenjun Chen and Corbett, {Alexandra J} and Eckle, {Sidonia B G} and Bronwyn Meehan and Yves d'Udekem and Konstantinov, {Igor E} and Martha Lappas and Ligong Liu and Goodnow, {Chris C} and Fairlie, {David P} and Jamie Rossjohn and Chong, {Mark M} and Katherine Kedzierska and Berzins, {Stuart P} and Belz, {Gabrielle T} and James McCluskey and Uldrich, {Adam P} and Godfrey, {Dale I} and Pellicci, {Daniel G}",
year = "2016",
month = "11",
doi = "10.1038/ni.3565",
language = "English",
volume = "17",
pages = "1300--1311",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "11",

}

Koay, H-F, Gherardin, NA, Enders, A, Loh, L, Mackay, LK, Almeida, CF, Russ, BE, Nold-Petry, CA, Nold, MF, Bedoui, S, Chen, Z, Corbett, AJ, Eckle, SBG, Meehan, B, d'Udekem, Y, Konstantinov, IE, Lappas, M, Liu, L, Goodnow, CC, Fairlie, DP, Rossjohn, J, Chong, MM, Kedzierska, K, Berzins, SP, Belz, GT, McCluskey, J, Uldrich, AP, Godfrey, DI & Pellicci, DG 2016, 'A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage' Nature Immunology, vol. 17, no. 11, pp. 1300-1311. https://doi.org/10.1038/ni.3565

A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. / Koay, Hui-Fern; Gherardin, Nicholas A; Enders, Anselm; Loh, Liyen; Mackay, Laura K; Almeida, Catarina F; Russ, Brendan E; Nold-Petry, Claudia A; Nold, Marcel F; Bedoui, Sammy; Chen, Zhenjun; Corbett, Alexandra J; Eckle, Sidonia B G; Meehan, Bronwyn; d'Udekem, Yves; Konstantinov, Igor E; Lappas, Martha; Liu, Ligong; Goodnow, Chris C; Fairlie, David P; Rossjohn, Jamie; Chong, Mark M; Kedzierska, Katherine; Berzins, Stuart P; Belz, Gabrielle T; McCluskey, James; Uldrich, Adam P; Godfrey, Dale I; Pellicci, Daniel G.

In: Nature Immunology, Vol. 17, No. 11, 11.2016, p. 1300-1311.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage

AU - Koay, Hui-Fern

AU - Gherardin, Nicholas A

AU - Enders, Anselm

AU - Loh, Liyen

AU - Mackay, Laura K

AU - Almeida, Catarina F

AU - Russ, Brendan E

AU - Nold-Petry, Claudia A

AU - Nold, Marcel F

AU - Bedoui, Sammy

AU - Chen, Zhenjun

AU - Corbett, Alexandra J

AU - Eckle, Sidonia B G

AU - Meehan, Bronwyn

AU - d'Udekem, Yves

AU - Konstantinov, Igor E

AU - Lappas, Martha

AU - Liu, Ligong

AU - Goodnow, Chris C

AU - Fairlie, David P

AU - Rossjohn, Jamie

AU - Chong, Mark M

AU - Kedzierska, Katherine

AU - Berzins, Stuart P

AU - Belz, Gabrielle T

AU - McCluskey, James

AU - Uldrich, Adam P

AU - Godfrey, Dale I

AU - Pellicci, Daniel G

PY - 2016/11

Y1 - 2016/11

N2 - Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.

AB - Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.

KW - innate immune cells

KW - mucosal immunology

UR - http://www.scopus.com/inward/record.url?scp=84988700978&partnerID=8YFLogxK

U2 - 10.1038/ni.3565

DO - 10.1038/ni.3565

M3 - Article

VL - 17

SP - 1300

EP - 1311

JO - Nature Immunology

JF - Nature Immunology

SN - 1529-2908

IS - 11

ER -

Koay H-F, Gherardin NA, Enders A, Loh L, Mackay LK, Almeida CF et al. A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. Nature Immunology. 2016 Nov;17(11):1300-1311. https://doi.org/10.1038/ni.3565