A network of high-mobility group box transcription factors programs innate interleukin-17 production

Nidhi Malhotra; Kavitha Narayan; Ok Hyun Cho; Katelyn Sylvia; Catherine C Yin; Heather J Melichar; Mehdi Rashighi; Veronique Lefebvre; John E Harris; Leslie J Berg; Joonsoo Kang; Emmanuel L Gautier; Claudia V Jakubzick; Gwendalyn J Randolph; J Adam Best; Jamie Knell; Ananda W Goldrath; Jennifer C Miller; Brian D Brown; Miriam Merad; Vladimir Jojic; Daphne Koller; Nadia R Cohen; Patrick J Brennan; Michael B Brenner; Tal Shay; Aviv Regev; Anne Fletcher; Kutlu G Elpek; Angelique Bellemare-Pelletier; Deepali Malhotra; Shannon J Turley; Radu Jianu; David H Laidlaw; Jim J Collins; Roi Gazit; Brian S Garrison; Derrick J Rossi; Francis S Kim; Tata N Rao; Amy Wagers; Susan A Shinton; Richard R Hardy; Paul Monach; Natalie A Bezman; Joseph C Sun; Charlie C Kim; Lewis L Lanier; Tracy S P Heng; Taras Kreslavsky; Michio W Painter; Jeffrey A Ericson; Scott P Davis; Diane Mathis; Christophe Benoist

doi:10.1016/j.immuni.2013.01.010

A network of high-mobility group box transcription factors programs innate interleukin-17 production

Nidhi Malhotra, Kavitha Narayan, Ok Hyun Cho, Katelyn Sylvia, Catherine C Yin, Heather J Melichar, Mehdi Rashighi, Veronique Lefebvre, John E Harris, Leslie J Berg, Joonsoo Kang, Emmanuel L Gautier, Claudia V Jakubzick, Gwendalyn J Randolph, J Adam Best, Jamie Knell, Ananda W Goldrath, Jennifer C Miller, Brian D Brown, Miriam MeradVladimir Jojic, Daphne Koller, Nadia R Cohen, Patrick J Brennan, Michael B Brenner, Tal Shay, Aviv Regev, Anne Fletcher, Kutlu G Elpek, Angelique Bellemare-Pelletier, Deepali Malhotra, Shannon J Turley, Radu Jianu, David H Laidlaw, Jim J Collins, Roi Gazit, Brian S Garrison, Derrick J Rossi, Francis S Kim, Tata N Rao, Amy Wagers, Susan A Shinton, Richard R Hardy, Paul Monach, Natalie A Bezman, Joseph C Sun, Charlie C Kim, Lewis L Lanier, Tracy S P Heng, Taras Kreslavsky, Michio W Painter, Jeffrey A Ericson, Scott P Davis, Diane Mathis, Christophe Benoist

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

141 Citations (Scopus)

Abstract

How innate lymphoid cells (ILCs) in the thymus and gut become specialized effectors is unclear. The prototypic innate-like gammadelta T cells (Tgammadelta17) are a major source of interleukin-17 (IL-17). We demonstrate that Tgammadelta17 cells are programmed by a gene regulatory network consisting of a quartet of high-mobility group (HMG) box transcription factors, SOX4, SOX13, TCF1, and LEF1, and not by conventional TCR signaling. SOX4 and SOX13 directly regulated the two requisite Tgammadelta17 cell-specific genes, Rorc and Blk, whereas TCF1 and LEF1 countered the SOX proteins and induced genes of alternate effector subsets. The T cell lineage specification factor TCF1 was also indispensable for the generation of IL-22 producing gut NKp46(+) ILCs and restrained cytokine production by lymphoid tissue inducer-like effectors. These results indicate that similar gene network architecture programs innate sources of IL-17, independent of anatomical origins.

Original language	English
Pages (from-to)	681 - 693
Number of pages	13
Journal	Immunity
Volume	38
Issue number	4
DOIs	https://doi.org/10.1016/j.immuni.2013.01.010
Publication status	Published - 2013
Externally published	Yes

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10.1016/j.immuni.2013.01.010

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Malhotra, N., Narayan, K., Cho, O. H., Sylvia, K., Yin, C. C., Melichar, H. J., Rashighi, M., Lefebvre, V., Harris, J. E., Berg, L. J., Kang, J., Gautier, E. L., Jakubzick, C. V., Randolph, G. J., Best, J. A., Knell, J., Goldrath, A. W., Miller, J. C., Brown, B. D., ... Benoist, C. (2013). A network of high-mobility group box transcription factors programs innate interleukin-17 production. Immunity, 38(4), 681 - 693. https://doi.org/10.1016/j.immuni.2013.01.010

@article{be9c2c0e1f384e4aa37d66971ff84f46,

title = "A network of high-mobility group box transcription factors programs innate interleukin-17 production",

abstract = "How innate lymphoid cells (ILCs) in the thymus and gut become specialized effectors is unclear. The prototypic innate-like gammadelta T cells (Tgammadelta17) are a major source of interleukin-17 (IL-17). We demonstrate that Tgammadelta17 cells are programmed by a gene regulatory network consisting of a quartet of high-mobility group (HMG) box transcription factors, SOX4, SOX13, TCF1, and LEF1, and not by conventional TCR signaling. SOX4 and SOX13 directly regulated the two requisite Tgammadelta17 cell-specific genes, Rorc and Blk, whereas TCF1 and LEF1 countered the SOX proteins and induced genes of alternate effector subsets. The T cell lineage specification factor TCF1 was also indispensable for the generation of IL-22 producing gut NKp46(+) ILCs and restrained cytokine production by lymphoid tissue inducer-like effectors. These results indicate that similar gene network architecture programs innate sources of IL-17, independent of anatomical origins.",

author = "Nidhi Malhotra and Kavitha Narayan and Cho, \{Ok Hyun\} and Katelyn Sylvia and Yin, \{Catherine C\} and Melichar, \{Heather J\} and Mehdi Rashighi and Veronique Lefebvre and Harris, \{John E\} and Berg, \{Leslie J\} and Joonsoo Kang and Gautier, \{Emmanuel L\} and Jakubzick, \{Claudia V\} and Randolph, \{Gwendalyn J\} and Best, \{J Adam\} and Jamie Knell and Goldrath, \{Ananda W\} and Miller, \{Jennifer C\} and Brown, \{Brian D\} and Miriam Merad and Vladimir Jojic and Daphne Koller and Cohen, \{Nadia R\} and Brennan, \{Patrick J\} and Brenner, \{Michael B\} and Tal Shay and Aviv Regev and Anne Fletcher and Elpek, \{Kutlu G\} and Angelique Bellemare-Pelletier and Deepali Malhotra and Turley, \{Shannon J\} and Radu Jianu and Laidlaw, \{David H\} and Collins, \{Jim J\} and Roi Gazit and Garrison, \{Brian S\} and Rossi, \{Derrick J\} and Kim, \{Francis S\} and Rao, \{Tata N\} and Amy Wagers and Shinton, \{Susan A\} and Hardy, \{Richard R\} and Paul Monach and Bezman, \{Natalie A\} and Sun, \{Joseph C\} and Kim, \{Charlie C\} and Lanier, \{Lewis L\} and Heng, \{Tracy S P\} and Taras Kreslavsky and Painter, \{Michio W\} and Ericson, \{Jeffrey A\} and Davis, \{Scott P\} and Diane Mathis and Christophe Benoist",

year = "2013",

doi = "10.1016/j.immuni.2013.01.010",

language = "English",

volume = "38",

pages = "681 -- 693",

journal = "Immunity",

issn = "1074-7613",

publisher = "Elsevier",

number = "4",

}

Malhotra, N, Narayan, K, Cho, OH, Sylvia, K, Yin, CC, Melichar, HJ, Rashighi, M, Lefebvre, V, Harris, JE, Berg, LJ, Kang, J, Gautier, EL, Jakubzick, CV, Randolph, GJ, Best, JA, Knell, J, Goldrath, AW, Miller, JC, Brown, BD, Merad, M, Jojic, V, Koller, D, Cohen, NR, Brennan, PJ, Brenner, MB, Shay, T, Regev, A, Fletcher, A, Elpek, KG, Bellemare-Pelletier, A, Malhotra, D, Turley, SJ, Jianu, R, Laidlaw, DH, Collins, JJ, Gazit, R, Garrison, BS, Rossi, DJ, Kim, FS, Rao, TN, Wagers, A, Shinton, SA, Hardy, RR, Monach, P, Bezman, NA, Sun, JC, Kim, CC, Lanier, LL, Heng, TSP, Kreslavsky, T, Painter, MW, Ericson, JA, Davis, SP, Mathis, D & Benoist, C 2013, 'A network of high-mobility group box transcription factors programs innate interleukin-17 production', Immunity, vol. 38, no. 4, pp. 681 - 693. https://doi.org/10.1016/j.immuni.2013.01.010

TY - JOUR

T1 - A network of high-mobility group box transcription factors programs innate interleukin-17 production

AU - Malhotra, Nidhi

AU - Narayan, Kavitha

AU - Cho, Ok Hyun

AU - Sylvia, Katelyn

AU - Yin, Catherine C

AU - Melichar, Heather J

AU - Rashighi, Mehdi

AU - Lefebvre, Veronique

AU - Harris, John E

AU - Berg, Leslie J

AU - Kang, Joonsoo

AU - Gautier, Emmanuel L

AU - Jakubzick, Claudia V

AU - Randolph, Gwendalyn J

AU - Best, J Adam

AU - Knell, Jamie

AU - Goldrath, Ananda W

AU - Miller, Jennifer C

AU - Brown, Brian D

AU - Merad, Miriam

AU - Jojic, Vladimir

AU - Koller, Daphne

AU - Cohen, Nadia R

AU - Brennan, Patrick J

AU - Brenner, Michael B

AU - Shay, Tal

AU - Regev, Aviv

AU - Fletcher, Anne

AU - Elpek, Kutlu G

AU - Bellemare-Pelletier, Angelique

AU - Malhotra, Deepali

AU - Turley, Shannon J

AU - Jianu, Radu

AU - Laidlaw, David H

AU - Collins, Jim J

AU - Gazit, Roi

AU - Garrison, Brian S

AU - Rossi, Derrick J

AU - Kim, Francis S

AU - Rao, Tata N

AU - Wagers, Amy

AU - Shinton, Susan A

AU - Hardy, Richard R

AU - Monach, Paul

AU - Bezman, Natalie A

AU - Sun, Joseph C

AU - Kim, Charlie C

AU - Lanier, Lewis L

AU - Heng, Tracy S P

AU - Kreslavsky, Taras

AU - Painter, Michio W

AU - Ericson, Jeffrey A

AU - Davis, Scott P

AU - Mathis, Diane

AU - Benoist, Christophe

PY - 2013

Y1 - 2013

N2 - How innate lymphoid cells (ILCs) in the thymus and gut become specialized effectors is unclear. The prototypic innate-like gammadelta T cells (Tgammadelta17) are a major source of interleukin-17 (IL-17). We demonstrate that Tgammadelta17 cells are programmed by a gene regulatory network consisting of a quartet of high-mobility group (HMG) box transcription factors, SOX4, SOX13, TCF1, and LEF1, and not by conventional TCR signaling. SOX4 and SOX13 directly regulated the two requisite Tgammadelta17 cell-specific genes, Rorc and Blk, whereas TCF1 and LEF1 countered the SOX proteins and induced genes of alternate effector subsets. The T cell lineage specification factor TCF1 was also indispensable for the generation of IL-22 producing gut NKp46(+) ILCs and restrained cytokine production by lymphoid tissue inducer-like effectors. These results indicate that similar gene network architecture programs innate sources of IL-17, independent of anatomical origins.

AB - How innate lymphoid cells (ILCs) in the thymus and gut become specialized effectors is unclear. The prototypic innate-like gammadelta T cells (Tgammadelta17) are a major source of interleukin-17 (IL-17). We demonstrate that Tgammadelta17 cells are programmed by a gene regulatory network consisting of a quartet of high-mobility group (HMG) box transcription factors, SOX4, SOX13, TCF1, and LEF1, and not by conventional TCR signaling. SOX4 and SOX13 directly regulated the two requisite Tgammadelta17 cell-specific genes, Rorc and Blk, whereas TCF1 and LEF1 countered the SOX proteins and induced genes of alternate effector subsets. The T cell lineage specification factor TCF1 was also indispensable for the generation of IL-22 producing gut NKp46(+) ILCs and restrained cytokine production by lymphoid tissue inducer-like effectors. These results indicate that similar gene network architecture programs innate sources of IL-17, independent of anatomical origins.

UR - http://www.ncbi.nlm.nih.gov/pubmed/23562159

UR - https://www.scopus.com/pages/publications/84876780175

U2 - 10.1016/j.immuni.2013.01.010

DO - 10.1016/j.immuni.2013.01.010

M3 - Article

SN - 1074-7613

VL - 38

SP - 681

EP - 693

JO - Immunity

JF - Immunity

IS - 4

ER -

A network of high-mobility group box transcription factors programs innate interleukin-17 production

Abstract

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