Information
References
Contents
Download
[1]TR Mosmann, H Cherwinski, MW Bond, MA Giedlin, RL Coffman: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136(7), 2348-2357 (1986)
[2]AK Abbas, KM Murphy, A Sher: Functional diversity of helper T lymphocytes. Nature 383, 787-793 (1996)
[3]SConstant, K Bottomly: Induction of TH1 and Th2 CD4 T cell responses: the alternative approaches. Annu Rev Immunol 15, 297-322 (1997)
[4]IC Ho, D Lo, LH Glimcher: c-maf promotes T helper cell type2 (Th2) and attenuates Th1 differentiation by both interleukin 4-dependent and-independent mechanisms. J Exp Med 188, 1859-1866 (1998)
[5]LGorelik, PE Fields, RA Flavell: Cutting edge: TGF-beta inhibits Th type2 development through inhibition of GATA-3 expression. J Immunol 165, 4773-4777 (2000)
[6]LGorelik, S Constant, RA Flavell. Mechanism of transforming growth factor beta-induced inhibition of T helper type1 differentiation. J Exp Med 195, 1499-1505 (2002)
[7]WChen, W Jin, N Hardegen, KJ Lei, L Li, N Marinos, G McGrady, SM Wahl: Conversion of peripheral CD4+CD25-naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198, 1875-1886 (2003)
[8]EBetteli, Y Carrier, W Gao, T Korn, TB Strom, M Oukka, HL Weiner, VK Kuchroo: Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235-238 (2006)
[9]EV Acosta-Rodriguez, G Napolitani, A Lanzavecchia, F Sallusto: Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8, 942-949 (2007)
[10]EBetteli, T Korn, VK Kuchroo: Th17: the third member of the effector T cell trilogy. Curr Opin Immunol 19, 652-657 (2007)
[11]II Ivanov, BS McKenie, L Zhou, CE Tadokoro, A Lepelley, JJ Lafaille, DJ Cua, DR Littman: The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121-1133 (2006).
[12]AN Mathur, HC Chang, DG Zisoulis, GL Stritesky, Q Yu, JT O’Malley, R Kapur, DE Levy, GS Kansas, MH Kaplan: Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol 178, 4901-4907 (2007).
[13]XO Yang, BP Pappu, R Nurieva, A Akimzhanov, HS Kang, Y Chung, L Ma, B Shah, AD Panopoulos, KS Schluns, SS Watowich, Q Tian, AM Jetten, C Dong: Thelper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28, 29-39 (2008)
[14]LZhou, II Ivanov, R Spolski, R Min, K Shenderov, T Egawa, DE Levy, WJ Leonard, DR Littman: IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8, 967-974 (2007)
[15]LHan, J Yang, X Wang, Q Wu, S Yin, Z Li, J Zhang, Y Xing, Z Chen, A Tsun, D Li, M Piccioni, Y Zhang, Q Guo, L Jiang, L Bao, L Lv, B Li: The E3 deubiquitinase USP17 is a positive regulator of retinoic acid-related orphan nuclear receptor γt (RORγt) in Th17 cells. J Biol Chem 289(37), 25546-25555 (2014)
[16]ALainé, B Martin, M Luka, L Mir, C Auffray, B Lucas, G Bismuth, C Charvet: Foxo1 Is a T Cell-Intrinsic Inhibitor of the RORγt-Th17 Program. J Immunol 195(4), 1791-1803 (2015)
[17]JSkepner, M Trocha, R Ramesh, XA Qu, D Schmidt, E Baloglu, M Lobera, S Davis, MA Nolan, TJ Carlson, J Hill, S Ghosh, MS Sundrud, J Yang: In vivo regulation of gene expression and T helper type17 differentiation by RORγt inverse agonists. Immunology 145(3), 347-256 (2015)
[18]SXiao, N Yosef, J Yang, Y Wang, L Zhou, C Zhu, C Wu, E Baloglu, D Schmidt, R Ramesh, M Lobera, MS Sundrud, PY Tsai, Z Xiang, J Wang, Y Xu, X Lin, K Kretschmer, PB Rahl, RA Young, Z Zhong, DA Hafler, A Regev, S Ghosh, A Marson, VK Kuchroo: Small-molecule RORγt antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms. Immunity 40(4), 477-489 (2014)
[19]MGanjalikhani Hakemi, K Ghaedi, V Homayouni, A Andalib, M Hosseini, A Rezaei: Positive and Negative Regulation of Th17 Cell Differentiation: Evaluating The Impact of RORC2. Cell J 16(3), 343-352 (2014)
[20]SNakae, Y Iwakura, H Suto, SJ Galli: Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17. J Leuk Bio 81, 1258-1268 (2007)
[21]GHuang, Y Wang, H Chi: Regulation of Th17 cell differentiation by innate immune signals. Cell Mol Immunol 9(4), 287–295 (2012)
[22]TKorn, E Bettelli, M Oukka, VK Kuchroo: IL-17 and Th17 Cells. Anna Rev Immunol 27, 485-517 (2009)
[23]ABrüstle, S Heink, M Huber, C Rosenplänter, C Stadelmann, P Yu, E Arpaia, TW Mak, T Kamradt, M Loboff: The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol 8, 958-966 (2007)
[24]QChen, W Yang, S Gupta, P Biswas, P Smith, G Bhagat, AB Pernis: IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor.Immunity 29:(6), 899-911 (2008)
[25]MHuber, A Brüstle, K Reinhard, A Guralnik, G Walter, A Mahiny, E von Löw, M Lohoff: IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype. Proc Natl Acad Sci USA 105, 20846-20851 (2008)
[26]YChung, SH Chang, GJ Martinez, XO Yang, R Nurieva, HS Kang, L Ma, SS Watowich, AM Jetten, Q Tian, C Dong: Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30, 576-587 (2009)
[27]DR Echlin, HJ Tae, N Mitin, EJ Taparowsky: B-ATF functions as a negative regulator of AP-1 mediated transcription and blocks cellular transformation by Ras and Fos. Oncogene 19, 1752-1763 (2000)
[28]GJ Martinez,RI Nurieva,XO Yang,C Dong: Regulation and function of proinflammatory Th17 cells.Ann N Y Acad Sci 1143, 188-211 (2008)
[29]GJ Martinez, C Dong: BATF: bringing (in) another Th17-regulating factor. J Mol Cell Biol 1, 66-68 (2009)
[30]BU Schraml, K Hildner, W Ise, WL Lee, WA Smith, B Solomon, G Sahota, J Sim, R Mukasa, S Cemerski, RD Hatton, GD Stormo, CT Weaver, JH Russell, TL Murphy, KM Murphy: The AP-1 transcription factor Batf controls T(H)17 differentiation. Nature 460, 405-409 (2009)
[31]IM Djuretic, D Levanon, V Negreanu, Y Groner, A Rao, KM Ansel: Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat immunol 8, 145-153 (2007)
[32]TEgawa, RE Tillman, Y Naoe, I Taniuchi, DR Littman: The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J Exp Med 204, 1945-1957 (2007)
[33]ACollins, DR Littman, I Taniuchi: RUNX proteins in transcription factor networks that regulate T-cell lineage choice. Nat Rev Immunol 9, 106-115 (2009)
[34]YWang, J Godec, K Ben-Aissa, K Cui, K Zhao, AB Pucsek, YK Lee, CT Weaver, R Yagi, V Lazarevic: The transcription factors T-bet and Runx are required for the ontogeny of pathogenic interferon-γ-producing T helper 17 cells. Immunity 40(3), 355-366 (2014)
[35]DMucida, Y Park, G Kim, O Turovskaya, I Scott, M Kronenberg, H Cheroutre: Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317, 256-260 (2007)
[36]MVeldhoen, K Hirota, AM Westendorf, J Buer, L Dumoutier, JC Renauld, B Stockinger: The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106-109 (2008)
[37]FJ Quintana, AS Basso, AH Iglesias, T Korn, MF Farez, E Bettelli, M Caccamo, M Oukka, HL Weiner: Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor. Nature 453, 65-71 (2008)
[38]EV Dang, J Barbi, HY Yang, D Jinasena, H Yu, Y Zheng, Z Bordman, J Fu, Y Kim, HR Yen, W Luo, K Zeller, L Shimoda, SL Topalian, GL Semenza, CV Dang, DM Pardoll, F Pan: Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 146, 772-784 (2011)
[39]LZhou, JE Lopes, MMW Chong, II Ivanov, R Min, GD Victora, Y Shen, J Du, YP Rubtsov, AY Rudensky, SF Ziegler, DR Littman: TGF-b-induced Foxp3 inhibits Th17 cell differentiation by antagonizing RORct function. Nature 453, 236-241 (2008)
[40]SJ Szabo, ST Kim, GL Costa, X Zhang, CG Fathman, LH Glimcher: Anovel transcription factor, T-bet, directs Th1 lineage commitment. Cell 1001, 655-669 (2000)
[41]VLazarevic, X Chen, JH Shim, ES Hwang, EJang, AN Bolm, M Oukka, VK Kuchroo, LH Glimcher: T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORgammat. Nat Immunol 121, 96-104 (2011)
[42]RNurieva, XO Yang, G Martinez, Y Zhang, AD Panopoulos, L Ma, K Schluns, Q Tian, SS Watowich, AM Jetten, C Dong: Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448, 480-483 (2007)
[43]XO Yang, AD Panopoulos, R Nurieva, SH Chang, D Wang, SS Watowich, C Dong: STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282, 9358-9363 (2007)
[44]TJ Harris, JF Grosso, HR Yen, H Xin, M Kortylewski, E Albesiano, EL Hipkiss, D Getnet, MV Goldberg, CH Maris, F Housseau, H Yu, DM Pardoll, CG Drake: Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol 179(7), 4313-4317 (2007)
[45]LDurant, WT Watford, HL Ramos, A Laurence, G Vahedi, L Wei, H Takahashi, HW Sun, Y Kanno, F Powrie, JJ O’Shea: Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32(5), 605-615 (2010)
[46]FChalmin, G Mignot, M Bruchard, A Chevriaux, F Vegran, A Hichami, S Ladoire, V Derangere, J Vincent, D Masson, SC Robson, G Eberl, JR ́ Pallandre, C Borg, B Ryffel, L Apetoh, C Rebe, F Ghiringhelli: Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression. Immunity 36, 362-373 (2012)
[47]JH Yoon, K Sudo, M Kuroda, M Kato, IK Lee, JS Han, S Nakae, T Imamura, J Kim, JH Ju, DK Kim, K Matsuzaki, M Weinstein, I Matsumoto, T Sumida, M Mamura: Phosphorylation status determines the opposing functions of Smad2/Smad3 as STAT3 cofactors in TH17 differentiation. Nat Commun 6, 7600 (2015)
[48]RDuhen,S Glatigny,CA Arbelaez,TC Blair,M Oukka,E Bettelli: Cutting edge: the pathogenicity of IFN-gamma-producing Th17 cells is independent of T-bet. J Immunol 190(9), 4478-4482 (2013)
[49]WT Watford, BD Hissong, JH Bream, Y Kanno, L Muul, JJ O’Shea: Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Immunol Rev 202, 139-156 (2004)
[50]ZYao, Y Kanno, M Kerenyi, G Stephens, L Durant, WT Watford, A Laurence, GW Robinson, EM Shevach, E Moriggl, L Hennighausen, C Wu, JJ O’Shea: Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood 109(10), 4368-4375 (2007)
[51]LKlotz, S Burgdorf, I Dani, K Saijo, J Flossdorf, S Hucke, J Alferink, N Nowak, M Beyer, G Mayer, B Langhans, T Klockgether, A Waisman, G Eberl, J Schultze, M Famulok, W Kolanus, C Glass, C Kurts, PA Knolle: The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity. J Exp Med 206, 2079-2089 (2009)
[52]BLi, JM Reynolds, RD Stout, DA Bernlohr, J Suttles: Regulation of Th17 differentiation by epidermal fatty acid-binding protein. J Immunol 182, 7625-7633 (2009)
Article Metrics
Download
- Contents
Information
Download
Contents
Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Genes associated with T helper 17 cell differentiation and function
1 Izmir Institute of Technology, Department of Molecular Biology and Genetics, Molecular Immunology and Gene Regulation Laboratory, Urla, İzmir, 35430 Turkey
*Author to whom correspondence should be addressed.
Abstract
Interleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector T helper cells that is distinct from the Th1 and Th2 CD4 phenotypes. In humans, Th17 differentiation is induced in the presence of the cytokines IL-1 beta, IL-6 and TGF beta, whereas IL-23 maintains Th17 survival. Effector human Th17 cells express several cytokines and cell surface markers, including IL-17A, IL-17F, IL-22, IL-26, CCR6 and TNFα. Studies on human cells have revealed that the RORC2 transcription factor plays an effective role in Th17 differentiation. Th17 cells contribute to the host immune response by involving various pathologies, including rheumatoid arthritis, multiple sclerosis and Crohn’s disease. However, the full extent of their contribution to diseases is being investigated.The differentiation of Th17 cells is controlled by many transcription factors, including ROR gammat, IRF4, RUNX1, BATF, and STAT3. This review covers the general principles of CD4 T helper differentiation and the known transcription factors that play a role in the recently discovered Th17 cells.
Keywords
- Th17
- Th17 Differentiation
- RORs
- IRF4
- BATF
- RUNX1
- FOXP3
- STATs
- Review
References
- [1] TR Mosmann, H Cherwinski, MW Bond, MA Giedlin, RL Coffman: Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136(7), 2348-2357 (1986)
- [2] AK Abbas, KM Murphy, A Sher: Functional diversity of helper T lymphocytes. Nature 383, 787-793 (1996)
- [3] SConstant, K Bottomly: Induction of TH1 and Th2 CD4 T cell responses: the alternative approaches. Annu Rev Immunol 15, 297-322 (1997)
- [4] IC Ho, D Lo, LH Glimcher: c-maf promotes T helper cell type2 (Th2) and attenuates Th1 differentiation by both interleukin 4-dependent and-independent mechanisms. J Exp Med 188, 1859-1866 (1998)
- [5] LGorelik, PE Fields, RA Flavell: Cutting edge: TGF-beta inhibits Th type2 development through inhibition of GATA-3 expression. J Immunol 165, 4773-4777 (2000)
- [6] LGorelik, S Constant, RA Flavell. Mechanism of transforming growth factor beta-induced inhibition of T helper type1 differentiation. J Exp Med 195, 1499-1505 (2002)
- [7] WChen, W Jin, N Hardegen, KJ Lei, L Li, N Marinos, G McGrady, SM Wahl: Conversion of peripheral CD4+CD25-naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198, 1875-1886 (2003)
- [8] EBetteli, Y Carrier, W Gao, T Korn, TB Strom, M Oukka, HL Weiner, VK Kuchroo: Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235-238 (2006)
- [9] EV Acosta-Rodriguez, G Napolitani, A Lanzavecchia, F Sallusto: Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8, 942-949 (2007)
- [10] EBetteli, T Korn, VK Kuchroo: Th17: the third member of the effector T cell trilogy. Curr Opin Immunol 19, 652-657 (2007)
- [11] II Ivanov, BS McKenie, L Zhou, CE Tadokoro, A Lepelley, JJ Lafaille, DJ Cua, DR Littman: The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121-1133 (2006).
- [12] AN Mathur, HC Chang, DG Zisoulis, GL Stritesky, Q Yu, JT O’Malley, R Kapur, DE Levy, GS Kansas, MH Kaplan: Stat3 and Stat4 direct development of IL-17-secreting Th cells. J Immunol 178, 4901-4907 (2007).
- [13] XO Yang, BP Pappu, R Nurieva, A Akimzhanov, HS Kang, Y Chung, L Ma, B Shah, AD Panopoulos, KS Schluns, SS Watowich, Q Tian, AM Jetten, C Dong: Thelper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28, 29-39 (2008)
- [14] LZhou, II Ivanov, R Spolski, R Min, K Shenderov, T Egawa, DE Levy, WJ Leonard, DR Littman: IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8, 967-974 (2007)
- [15] LHan, J Yang, X Wang, Q Wu, S Yin, Z Li, J Zhang, Y Xing, Z Chen, A Tsun, D Li, M Piccioni, Y Zhang, Q Guo, L Jiang, L Bao, L Lv, B Li: The E3 deubiquitinase USP17 is a positive regulator of retinoic acid-related orphan nuclear receptor γt (RORγt) in Th17 cells. J Biol Chem 289(37), 25546-25555 (2014)
- [16] ALainé, B Martin, M Luka, L Mir, C Auffray, B Lucas, G Bismuth, C Charvet: Foxo1 Is a T Cell-Intrinsic Inhibitor of the RORγt-Th17 Program. J Immunol 195(4), 1791-1803 (2015)
- [17] JSkepner, M Trocha, R Ramesh, XA Qu, D Schmidt, E Baloglu, M Lobera, S Davis, MA Nolan, TJ Carlson, J Hill, S Ghosh, MS Sundrud, J Yang: In vivo regulation of gene expression and T helper type17 differentiation by RORγt inverse agonists. Immunology 145(3), 347-256 (2015)
- [18] SXiao, N Yosef, J Yang, Y Wang, L Zhou, C Zhu, C Wu, E Baloglu, D Schmidt, R Ramesh, M Lobera, MS Sundrud, PY Tsai, Z Xiang, J Wang, Y Xu, X Lin, K Kretschmer, PB Rahl, RA Young, Z Zhong, DA Hafler, A Regev, S Ghosh, A Marson, VK Kuchroo: Small-molecule RORγt antagonists inhibit T helper 17 cell transcriptional network by divergent mechanisms. Immunity 40(4), 477-489 (2014)
- [19] MGanjalikhani Hakemi, K Ghaedi, V Homayouni, A Andalib, M Hosseini, A Rezaei: Positive and Negative Regulation of Th17 Cell Differentiation: Evaluating The Impact of RORC2. Cell J 16(3), 343-352 (2014)
- [20] SNakae, Y Iwakura, H Suto, SJ Galli: Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17. J Leuk Bio 81, 1258-1268 (2007)
- [21] GHuang, Y Wang, H Chi: Regulation of Th17 cell differentiation by innate immune signals. Cell Mol Immunol 9(4), 287–295 (2012)
- [22] TKorn, E Bettelli, M Oukka, VK Kuchroo: IL-17 and Th17 Cells. Anna Rev Immunol 27, 485-517 (2009)
- [23] ABrüstle, S Heink, M Huber, C Rosenplänter, C Stadelmann, P Yu, E Arpaia, TW Mak, T Kamradt, M Loboff: The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4. Nat Immunol 8, 958-966 (2007)
- [24] QChen, W Yang, S Gupta, P Biswas, P Smith, G Bhagat, AB Pernis: IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor.Immunity 29:(6), 899-911 (2008)
- [25] MHuber, A Brüstle, K Reinhard, A Guralnik, G Walter, A Mahiny, E von Löw, M Lohoff: IRF4 is essential for IL-21-mediated induction, amplification, and stabilization of the Th17 phenotype. Proc Natl Acad Sci USA 105, 20846-20851 (2008)
- [26] YChung, SH Chang, GJ Martinez, XO Yang, R Nurieva, HS Kang, L Ma, SS Watowich, AM Jetten, Q Tian, C Dong: Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30, 576-587 (2009)
- [27] DR Echlin, HJ Tae, N Mitin, EJ Taparowsky: B-ATF functions as a negative regulator of AP-1 mediated transcription and blocks cellular transformation by Ras and Fos. Oncogene 19, 1752-1763 (2000)
- [28] GJ Martinez,RI Nurieva,XO Yang,C Dong: Regulation and function of proinflammatory Th17 cells.Ann N Y Acad Sci 1143, 188-211 (2008)
- [29] GJ Martinez, C Dong: BATF: bringing (in) another Th17-regulating factor. J Mol Cell Biol 1, 66-68 (2009)
- [30] BU Schraml, K Hildner, W Ise, WL Lee, WA Smith, B Solomon, G Sahota, J Sim, R Mukasa, S Cemerski, RD Hatton, GD Stormo, CT Weaver, JH Russell, TL Murphy, KM Murphy: The AP-1 transcription factor Batf controls T(H)17 differentiation. Nature 460, 405-409 (2009)
- [31] IM Djuretic, D Levanon, V Negreanu, Y Groner, A Rao, KM Ansel: Transcription factors T-bet and Runx3 cooperate to activate Ifng and silence Il4 in T helper type 1 cells. Nat immunol 8, 145-153 (2007)
- [32] TEgawa, RE Tillman, Y Naoe, I Taniuchi, DR Littman: The role of the Runx transcription factors in thymocyte differentiation and in homeostasis of naive T cells. J Exp Med 204, 1945-1957 (2007)
- [33] ACollins, DR Littman, I Taniuchi: RUNX proteins in transcription factor networks that regulate T-cell lineage choice. Nat Rev Immunol 9, 106-115 (2009)
- [34] YWang, J Godec, K Ben-Aissa, K Cui, K Zhao, AB Pucsek, YK Lee, CT Weaver, R Yagi, V Lazarevic: The transcription factors T-bet and Runx are required for the ontogeny of pathogenic interferon-γ-producing T helper 17 cells. Immunity 40(3), 355-366 (2014)
- [35] DMucida, Y Park, G Kim, O Turovskaya, I Scott, M Kronenberg, H Cheroutre: Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317, 256-260 (2007)
- [36] MVeldhoen, K Hirota, AM Westendorf, J Buer, L Dumoutier, JC Renauld, B Stockinger: The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106-109 (2008)
- [37] FJ Quintana, AS Basso, AH Iglesias, T Korn, MF Farez, E Bettelli, M Caccamo, M Oukka, HL Weiner: Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor. Nature 453, 65-71 (2008)
- [38] EV Dang, J Barbi, HY Yang, D Jinasena, H Yu, Y Zheng, Z Bordman, J Fu, Y Kim, HR Yen, W Luo, K Zeller, L Shimoda, SL Topalian, GL Semenza, CV Dang, DM Pardoll, F Pan: Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell 146, 772-784 (2011)
- [39] LZhou, JE Lopes, MMW Chong, II Ivanov, R Min, GD Victora, Y Shen, J Du, YP Rubtsov, AY Rudensky, SF Ziegler, DR Littman: TGF-b-induced Foxp3 inhibits Th17 cell differentiation by antagonizing RORct function. Nature 453, 236-241 (2008)
- [40] SJ Szabo, ST Kim, GL Costa, X Zhang, CG Fathman, LH Glimcher: Anovel transcription factor, T-bet, directs Th1 lineage commitment. Cell 1001, 655-669 (2000)
- [41] VLazarevic, X Chen, JH Shim, ES Hwang, EJang, AN Bolm, M Oukka, VK Kuchroo, LH Glimcher: T-bet represses T(H)17 differentiation by preventing Runx1-mediated activation of the gene encoding RORgammat. Nat Immunol 121, 96-104 (2011)
- [42] RNurieva, XO Yang, G Martinez, Y Zhang, AD Panopoulos, L Ma, K Schluns, Q Tian, SS Watowich, AM Jetten, C Dong: Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448, 480-483 (2007)
- [43] XO Yang, AD Panopoulos, R Nurieva, SH Chang, D Wang, SS Watowich, C Dong: STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282, 9358-9363 (2007)
- [44] TJ Harris, JF Grosso, HR Yen, H Xin, M Kortylewski, E Albesiano, EL Hipkiss, D Getnet, MV Goldberg, CH Maris, F Housseau, H Yu, DM Pardoll, CG Drake: Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol 179(7), 4313-4317 (2007)
- [45] LDurant, WT Watford, HL Ramos, A Laurence, G Vahedi, L Wei, H Takahashi, HW Sun, Y Kanno, F Powrie, JJ O’Shea: Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity 32(5), 605-615 (2010)
- [46] FChalmin, G Mignot, M Bruchard, A Chevriaux, F Vegran, A Hichami, S Ladoire, V Derangere, J Vincent, D Masson, SC Robson, G Eberl, JR ́ Pallandre, C Borg, B Ryffel, L Apetoh, C Rebe, F Ghiringhelli: Stat3 and Gfi-1 Transcription Factors Control Th17 Cell Immunosuppressive Activity via the Regulation of Ectonucleotidase Expression. Immunity 36, 362-373 (2012)
- [47] JH Yoon, K Sudo, M Kuroda, M Kato, IK Lee, JS Han, S Nakae, T Imamura, J Kim, JH Ju, DK Kim, K Matsuzaki, M Weinstein, I Matsumoto, T Sumida, M Mamura: Phosphorylation status determines the opposing functions of Smad2/Smad3 as STAT3 cofactors in TH17 differentiation. Nat Commun 6, 7600 (2015)
- [48] RDuhen,S Glatigny,CA Arbelaez,TC Blair,M Oukka,E Bettelli: Cutting edge: the pathogenicity of IFN-gamma-producing Th17 cells is independent of T-bet. J Immunol 190(9), 4478-4482 (2013)
- [49] WT Watford, BD Hissong, JH Bream, Y Kanno, L Muul, JJ O’Shea: Signaling by IL-12 and IL-23 and the immunoregulatory roles of STAT4. Immunol Rev 202, 139-156 (2004)
- [50] ZYao, Y Kanno, M Kerenyi, G Stephens, L Durant, WT Watford, A Laurence, GW Robinson, EM Shevach, E Moriggl, L Hennighausen, C Wu, JJ O’Shea: Nonredundant roles for Stat5a/b in directly regulating Foxp3. Blood 109(10), 4368-4375 (2007)
- [51] LKlotz, S Burgdorf, I Dani, K Saijo, J Flossdorf, S Hucke, J Alferink, N Nowak, M Beyer, G Mayer, B Langhans, T Klockgether, A Waisman, G Eberl, J Schultze, M Famulok, W Kolanus, C Glass, C Kurts, PA Knolle: The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity. J Exp Med 206, 2079-2089 (2009)
- [52] BLi, JM Reynolds, RD Stout, DA Bernlohr, J Suttles: Regulation of Th17 differentiation by epidermal fatty acid-binding protein. J Immunol 182, 7625-7633 (2009)
