Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes

Kavitha Narayan; Katelyn E. Sylvia; Nidhi Malhotra; Catherine C. Yin; Gregory Martens; Therese Vallerskog; Hardy Kornfeld; Na Xiong; Nadia R. Cohen; Michael B. Brenner; Leslie J. Berg; Joonsoo Kang; Yan Zhou; Susan A. Shinton; Richard R. Hardy; Natalie A. Bezman; Joseph C. Sun; Charlie C. Kim; Lewis L. Lanier; Jennifer Miller; Brian Brown; Miriam Merad; Anne Fletcher; Kutlu Elpek; Angelique Bellemare-Pelletier; Deepali Malhotra; Shannon Turley; Katelyn Sylvia; Roi Gazit; Brian Garrison; Derrick J. Rossi; Vladimir Jojic; Daphne Koller; Radu Jianu; David Laidlaw; James Costello; Jim Collins; Nadia Cohen; Patrick Brennan; Michael Brenner; Tal Shay; Aviv Regev; Francis Kim; Tata Nageswara Rao; Amy Wagers; Emmanuel L. Gautier; Claudia Jakubzick; Gwendalyn J. Randolph; Paul Monach; Adam J. Best; Jamie Knell; Ananda Goldrath; Tracy Heng; Taras Kreslavsky; Michio Painter; Diane Mathis; Christophe Benoist

doi:10.1038/ni.2247

Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes

Kavitha Narayan, Katelyn E. Sylvia, Nidhi Malhotra, Catherine C. Yin, Gregory Martens, Therese Vallerskog, Hardy Kornfeld, Na Xiong, Nadia R. Cohen, Michael B. Brenner, Leslie J. Berg, Joonsoo Kang, Yan Zhou, Susan A. Shinton, Richard R. Hardy, Natalie A. Bezman, Joseph C. Sun, Charlie C. Kim, Lewis L. Lanier, Jennifer MillerBrian Brown, Miriam Merad, Anne Fletcher, Kutlu Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon Turley, Katelyn Sylvia, Roi Gazit, Brian Garrison, Derrick J. Rossi, Vladimir Jojic, Daphne Koller, Radu Jianu, David Laidlaw, James Costello, Jim Collins, Nadia Cohen, Patrick Brennan, Michael Brenner, Tal Shay, Aviv Regev, Francis Kim, Tata Nageswara Rao, Amy Wagers, Emmanuel L. Gautier, Claudia Jakubzick, Gwendalyn J. Randolph, Paul Monach, Adam J. Best, Jamie Knell, Ananda Goldrath, Tracy Heng, Taras Kreslavsky, Michio Painter, Diane Mathis, Christophe Benoist

Research output: Contribution to journal › Article › peer-review

170 Scopus citations

Abstract

Innate γδ T cells function in the early phase of immune responses. Although innate γδ T cells have often been studied as one homogenous population, they can be functionally classified into effector subsets on the basis of the production of signature cytokines, analogous to adaptive helper T cell subsets. However, unlike the function of adaptive T cells, γδ effector T cell function correlates with genomically encoded T cell antigen receptor (TCR) chains, which suggests that clonal TCR selection is not the main determinant of the differentiation of γδ effector cells. A high-resolution transcriptome analysis of all emergent γδ thymocyte subsets segregated on the basis of use of the TCR γchain or δ-chain indicated the existence of three separate subtypes of γδ effector cells in the thymus. The immature γδ subsets were distinguished by unique transcription-factor modules that program effector function.

Original language	English (US)
Pages (from-to)	511-518
Number of pages	8
Journal	Nature Immunology
Volume	13
Issue number	5
DOIs	https://doi.org/10.1038/ni.2247
State	Published - May 2012

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Immunology

Access to Document

10.1038/ni.2247

Cite this

Narayan, K., Sylvia, K. E., Malhotra, N., Yin, C. C., Martens, G., Vallerskog, T., Kornfeld, H., Xiong, N., Cohen, N. R., Brenner, M. B., Berg, L. J., Kang, J., Zhou, Y., Shinton, S. A., Hardy, R. R., Bezman, N. A., Sun, J. C., Kim, C. C., Lanier, L. L., ... Benoist, C. (2012). Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes. Nature Immunology, 13(5), 511-518. https://doi.org/10.1038/ni.2247

@article{ea3522d908f54af9867e2efc55d22d82,

title = "Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes",

abstract = "Innate γδ T cells function in the early phase of immune responses. Although innate γδ T cells have often been studied as one homogenous population, they can be functionally classified into effector subsets on the basis of the production of signature cytokines, analogous to adaptive helper T cell subsets. However, unlike the function of adaptive T cells, γδ effector T cell function correlates with genomically encoded T cell antigen receptor (TCR) chains, which suggests that clonal TCR selection is not the main determinant of the differentiation of γδ effector cells. A high-resolution transcriptome analysis of all emergent γδ thymocyte subsets segregated on the basis of use of the TCR γchain or δ-chain indicated the existence of three separate subtypes of γδ effector cells in the thymus. The immature γδ subsets were distinguished by unique transcription-factor modules that program effector function.",

author = "Kavitha Narayan and Sylvia, {Katelyn E.} and Nidhi Malhotra and Yin, {Catherine C.} and Gregory Martens and Therese Vallerskog and Hardy Kornfeld and Na Xiong and Cohen, {Nadia R.} and Brenner, {Michael B.} and Berg, {Leslie J.} and Joonsoo Kang and Yan Zhou and Shinton, {Susan A.} and Hardy, {Richard R.} and Bezman, {Natalie A.} and Sun, {Joseph C.} and Kim, {Charlie C.} and Lanier, {Lewis L.} and Jennifer Miller and Brian Brown and Miriam Merad and Anne Fletcher and Kutlu Elpek and Angelique Bellemare-Pelletier and Deepali Malhotra and Shannon Turley and Katelyn Sylvia and Roi Gazit and Brian Garrison and Rossi, {Derrick J.} and Vladimir Jojic and Daphne Koller and Radu Jianu and David Laidlaw and James Costello and Jim Collins and Nadia Cohen and Patrick Brennan and Michael Brenner and Tal Shay and Aviv Regev and Francis Kim and Rao, {Tata Nageswara} and Amy Wagers and Gautier, {Emmanuel L.} and Claudia Jakubzick and Randolph, {Gwendalyn J.} and Paul Monach and Best, {Adam J.} and Jamie Knell and Ananda Goldrath and Tracy Heng and Taras Kreslavsky and Michio Painter and Diane Mathis and Christophe Benoist",

note = "Funding Information: We thank M. Mohrs (Trudeau Institute) for IL-4–GFP reporter mice; H. Birchmeier (Max-Delbr{\"u}ck-Center for Molecular Medicine Berlin) for Axin2 reporter mice; V. Lefebvre (Cleveland Clinic) for Sox5 reporter mice; K. Rock (University of Massachusetts Medical School) for Ctsl−/− mice; E. Huseby (University of Massachusetts Medical School) for Cd74−/− mice; S. Davis (Harvard Medical School) for the ConsolidateProbeSets module and PopulationDistances PCA program; A. Hayday (King{\textquoteright}s College, London) for anti-Vδ1 (17D1); members of the ImmGen Consortium for discussions; the ImmGen core team (M. Painter, J. Ericson and S. Davis) for help with data generation and processing; and eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project. Core resources supported by the Diabetes Endocrinology Research Center (DK32520) were used. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R24 AI072073 to the ImmGen group, and CA100382 to J.K.).",

year = "2012",

month = may,

doi = "10.1038/ni.2247",

language = "English (US)",

volume = "13",

pages = "511--518",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Research",

number = "5",

}

Narayan, K, Sylvia, KE, Malhotra, N, Yin, CC, Martens, G, Vallerskog, T, Kornfeld, H, Xiong, N, Cohen, NR, Brenner, MB, Berg, LJ, Kang, J, Zhou, Y, Shinton, SA, Hardy, RR, Bezman, NA, Sun, JC, Kim, CC, Lanier, LL, Miller, J, Brown, B, Merad, M, Fletcher, A, Elpek, K, Bellemare-Pelletier, A, Malhotra, D, Turley, S, Sylvia, K, Gazit, R, Garrison, B, Rossi, DJ, Jojic, V, Koller, D, Jianu, R, Laidlaw, D, Costello, J, Collins, J, Cohen, N, Brennan, P, Brenner, M, Shay, T, Regev, A, Kim, F, Rao, TN, Wagers, A, Gautier, EL, Jakubzick, C, Randolph, GJ, Monach, P, Best, AJ, Knell, J, Goldrath, A, Heng, T, Kreslavsky, T, Painter, M, Mathis, D & Benoist, C 2012, 'Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes', Nature Immunology, vol. 13, no. 5, pp. 511-518. https://doi.org/10.1038/ni.2247

TY - JOUR

T1 - Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes

AU - Narayan, Kavitha

AU - Sylvia, Katelyn E.

AU - Malhotra, Nidhi

AU - Yin, Catherine C.

AU - Martens, Gregory

AU - Vallerskog, Therese

AU - Kornfeld, Hardy

AU - Xiong, Na

AU - Cohen, Nadia R.

AU - Brenner, Michael B.

AU - Berg, Leslie J.

AU - Kang, Joonsoo

AU - Zhou, Yan

AU - Shinton, Susan A.

AU - Hardy, Richard R.

AU - Bezman, Natalie A.

AU - Sun, Joseph C.

AU - Kim, Charlie C.

AU - Lanier, Lewis L.

AU - Miller, Jennifer

AU - Brown, Brian

AU - Merad, Miriam

AU - Fletcher, Anne

AU - Elpek, Kutlu

AU - Bellemare-Pelletier, Angelique

AU - Malhotra, Deepali

AU - Turley, Shannon

AU - Sylvia, Katelyn

AU - Gazit, Roi

AU - Garrison, Brian

AU - Rossi, Derrick J.

AU - Jojic, Vladimir

AU - Koller, Daphne

AU - Jianu, Radu

AU - Laidlaw, David

AU - Costello, James

AU - Collins, Jim

AU - Cohen, Nadia

AU - Brennan, Patrick

AU - Brenner, Michael

AU - Shay, Tal

AU - Regev, Aviv

AU - Kim, Francis

AU - Rao, Tata Nageswara

AU - Wagers, Amy

AU - Gautier, Emmanuel L.

AU - Jakubzick, Claudia

AU - Randolph, Gwendalyn J.

AU - Monach, Paul

AU - Best, Adam J.

AU - Knell, Jamie

AU - Goldrath, Ananda

AU - Heng, Tracy

AU - Kreslavsky, Taras

AU - Painter, Michio

AU - Mathis, Diane

AU - Benoist, Christophe

N1 - Funding Information: We thank M. Mohrs (Trudeau Institute) for IL-4–GFP reporter mice; H. Birchmeier (Max-Delbrück-Center for Molecular Medicine Berlin) for Axin2 reporter mice; V. Lefebvre (Cleveland Clinic) for Sox5 reporter mice; K. Rock (University of Massachusetts Medical School) for Ctsl−/− mice; E. Huseby (University of Massachusetts Medical School) for Cd74−/− mice; S. Davis (Harvard Medical School) for the ConsolidateProbeSets module and PopulationDistances PCA program; A. Hayday (King’s College, London) for anti-Vδ1 (17D1); members of the ImmGen Consortium for discussions; the ImmGen core team (M. Painter, J. Ericson and S. Davis) for help with data generation and processing; and eBioscience, Affymetrix and Expression Analysis for support of the ImmGen Project. Core resources supported by the Diabetes Endocrinology Research Center (DK32520) were used. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R24 AI072073 to the ImmGen group, and CA100382 to J.K.).

PY - 2012/5

Y1 - 2012/5

N2 - Innate γδ T cells function in the early phase of immune responses. Although innate γδ T cells have often been studied as one homogenous population, they can be functionally classified into effector subsets on the basis of the production of signature cytokines, analogous to adaptive helper T cell subsets. However, unlike the function of adaptive T cells, γδ effector T cell function correlates with genomically encoded T cell antigen receptor (TCR) chains, which suggests that clonal TCR selection is not the main determinant of the differentiation of γδ effector cells. A high-resolution transcriptome analysis of all emergent γδ thymocyte subsets segregated on the basis of use of the TCR γchain or δ-chain indicated the existence of three separate subtypes of γδ effector cells in the thymus. The immature γδ subsets were distinguished by unique transcription-factor modules that program effector function.

AB - Innate γδ T cells function in the early phase of immune responses. Although innate γδ T cells have often been studied as one homogenous population, they can be functionally classified into effector subsets on the basis of the production of signature cytokines, analogous to adaptive helper T cell subsets. However, unlike the function of adaptive T cells, γδ effector T cell function correlates with genomically encoded T cell antigen receptor (TCR) chains, which suggests that clonal TCR selection is not the main determinant of the differentiation of γδ effector cells. A high-resolution transcriptome analysis of all emergent γδ thymocyte subsets segregated on the basis of use of the TCR γchain or δ-chain indicated the existence of three separate subtypes of γδ effector cells in the thymus. The immature γδ subsets were distinguished by unique transcription-factor modules that program effector function.

UR - http://www.scopus.com/inward/record.url?scp=84859890898&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859890898&partnerID=8YFLogxK

U2 - 10.1038/ni.2247

DO - 10.1038/ni.2247

M3 - Article

C2 - 22473038

AN - SCOPUS:84859890898

SN - 1529-2908

VL - 13

SP - 511

EP - 518

JO - Nature Immunology

JF - Nature Immunology

IS - 5

ER -

Intrathymic programming of effector fates in three molecularly distinct γδ T cell subtypes

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this