Induction and transcriptional regulation of the co-inhibitory gene module in T cells

Research output: Contribution to journalArticlepeer-review

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Induction and transcriptional regulation of the co-inhibitory gene module in T cells. / Chihara, Norio; Madi, Asaf ; Kondo, Takaaki ; Zhang, Huiyuan ; Acharya, Nandini ; Singer, Meromit ; Nyman, Jackson ; Marjanovic, Nemanja D. ; Kowalczyk, Monika S. ; Wang, Chao ; Kurtulus, Sema ; Law, Travis ; Etminan, Yasaman ; Nevin, James ; Buckley, Christopher; Burkett, Patrick R. ; Buenrostro, Jason D. ; Rozenblatt-Rosen, Orit ; Anderson, Ana C. ; Regev, Aviv; Kuchroo, Vijay K. .

In: Nature, Vol. 558, No. 7710 , 21.06.2018, p. 454–459.

Research output: Contribution to journalArticlepeer-review

Harvard

Chihara, N, Madi, A, Kondo, T, Zhang, H, Acharya, N, Singer, M, Nyman, J, Marjanovic, ND, Kowalczyk, MS, Wang, C, Kurtulus, S, Law, T, Etminan, Y, Nevin, J, Buckley, C, Burkett, PR, Buenrostro, JD, Rozenblatt-Rosen, O, Anderson, AC, Regev, A & Kuchroo, VK 2018, 'Induction and transcriptional regulation of the co-inhibitory gene module in T cells', Nature, vol. 558, no. 7710 , pp. 454–459. https://doi.org/10.1038/s41586-018-0206-z

APA

Chihara, N., Madi, A., Kondo, T., Zhang, H., Acharya, N., Singer, M., Nyman, J., Marjanovic, N. D., Kowalczyk, M. S., Wang, C., Kurtulus, S., Law, T., Etminan, Y., Nevin, J., Buckley, C., Burkett, P. R., Buenrostro, J. D., Rozenblatt-Rosen, O., Anderson, A. C., ... Kuchroo, V. K. (2018). Induction and transcriptional regulation of the co-inhibitory gene module in T cells. Nature, 558(7710 ), 454–459. https://doi.org/10.1038/s41586-018-0206-z

Vancouver

Chihara N, Madi A, Kondo T, Zhang H, Acharya N, Singer M et al. Induction and transcriptional regulation of the co-inhibitory gene module in T cells. Nature. 2018 Jun 21;558(7710 ):454–459. https://doi.org/10.1038/s41586-018-0206-z

Author

Chihara, Norio ; Madi, Asaf ; Kondo, Takaaki ; Zhang, Huiyuan ; Acharya, Nandini ; Singer, Meromit ; Nyman, Jackson ; Marjanovic, Nemanja D. ; Kowalczyk, Monika S. ; Wang, Chao ; Kurtulus, Sema ; Law, Travis ; Etminan, Yasaman ; Nevin, James ; Buckley, Christopher ; Burkett, Patrick R. ; Buenrostro, Jason D. ; Rozenblatt-Rosen, Orit ; Anderson, Ana C. ; Regev, Aviv ; Kuchroo, Vijay K. . / Induction and transcriptional regulation of the co-inhibitory gene module in T cells. In: Nature. 2018 ; Vol. 558, No. 7710 . pp. 454–459.

Bibtex

@article{d6ec5d1cdef7482198514e49af933c83,
title = "Induction and transcriptional regulation of the co-inhibitory gene module in T cells",
abstract = "The expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated expression of co-inhibitory receptors on CD4+ T cells promotes autoimmunity, whereas sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and diseases such as cancer. Here, using RNA and protein expression profiling at single-cell resolution in mouse cells, we identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, TIM-3, LAG-3 and TIGIT) but also many new surface receptors. We functionally validated two new co-inhibitory receptors, activated protein C receptor (PROCR) and podoplanin (PDPN). The module of co-inhibitory receptors is co-expressed in both CD4+ and CD8+ T cells and is part of a larger co-inhibitory gene program that is shared by non-responsive T cells in several physiological contexts and is driven by the immunoregulatory cytokine IL-27. Computational analysis identified the transcription factors PRDM1 and c-MAF as cooperative regulators of the co-inhibitory module, and this was validated experimentally. This molecular circuit underlies the co-expression of co-inhibitory receptors in T cells and identifies regulators of T cell function with the potential to control autoimmunity and tumour immunity.",
author = "Norio Chihara and Asaf Madi and Takaaki Kondo and Huiyuan Zhang and Nandini Acharya and Meromit Singer and Jackson Nyman and Marjanovic, {Nemanja D.} and Kowalczyk, {Monika S.} and Chao Wang and Sema Kurtulus and Travis Law and Yasaman Etminan and James Nevin and Christopher Buckley and Burkett, {Patrick R.} and Buenrostro, {Jason D.} and Orit Rozenblatt-Rosen and Anderson, {Ana C.} and Aviv Regev and Kuchroo, {Vijay K.}",
year = "2018",
month = jun,
day = "21",
doi = "10.1038/s41586-018-0206-z",
language = "English",
volume = "558",
pages = "454–459",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7710 ",

}

RIS

TY - JOUR

T1 - Induction and transcriptional regulation of the co-inhibitory gene module in T cells

AU - Chihara, Norio

AU - Madi, Asaf

AU - Kondo, Takaaki

AU - Zhang, Huiyuan

AU - Acharya, Nandini

AU - Singer, Meromit

AU - Nyman, Jackson

AU - Marjanovic, Nemanja D.

AU - Kowalczyk, Monika S.

AU - Wang, Chao

AU - Kurtulus, Sema

AU - Law, Travis

AU - Etminan, Yasaman

AU - Nevin, James

AU - Buckley, Christopher

AU - Burkett, Patrick R.

AU - Buenrostro, Jason D.

AU - Rozenblatt-Rosen, Orit

AU - Anderson, Ana C.

AU - Regev, Aviv

AU - Kuchroo, Vijay K.

PY - 2018/6/21

Y1 - 2018/6/21

N2 - The expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated expression of co-inhibitory receptors on CD4+ T cells promotes autoimmunity, whereas sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and diseases such as cancer. Here, using RNA and protein expression profiling at single-cell resolution in mouse cells, we identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, TIM-3, LAG-3 and TIGIT) but also many new surface receptors. We functionally validated two new co-inhibitory receptors, activated protein C receptor (PROCR) and podoplanin (PDPN). The module of co-inhibitory receptors is co-expressed in both CD4+ and CD8+ T cells and is part of a larger co-inhibitory gene program that is shared by non-responsive T cells in several physiological contexts and is driven by the immunoregulatory cytokine IL-27. Computational analysis identified the transcription factors PRDM1 and c-MAF as cooperative regulators of the co-inhibitory module, and this was validated experimentally. This molecular circuit underlies the co-expression of co-inhibitory receptors in T cells and identifies regulators of T cell function with the potential to control autoimmunity and tumour immunity.

AB - The expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated expression of co-inhibitory receptors on CD4+ T cells promotes autoimmunity, whereas sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and diseases such as cancer. Here, using RNA and protein expression profiling at single-cell resolution in mouse cells, we identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, TIM-3, LAG-3 and TIGIT) but also many new surface receptors. We functionally validated two new co-inhibitory receptors, activated protein C receptor (PROCR) and podoplanin (PDPN). The module of co-inhibitory receptors is co-expressed in both CD4+ and CD8+ T cells and is part of a larger co-inhibitory gene program that is shared by non-responsive T cells in several physiological contexts and is driven by the immunoregulatory cytokine IL-27. Computational analysis identified the transcription factors PRDM1 and c-MAF as cooperative regulators of the co-inhibitory module, and this was validated experimentally. This molecular circuit underlies the co-expression of co-inhibitory receptors in T cells and identifies regulators of T cell function with the potential to control autoimmunity and tumour immunity.

U2 - 10.1038/s41586-018-0206-z

DO - 10.1038/s41586-018-0206-z

M3 - Article

VL - 558

SP - 454

EP - 459

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7710

ER -