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

133 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

Access to Document

10.1016/j.immuni.2013.01.010

Cite this

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

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

Access to Document

Other files and links

Cite this