Fate mapping of IL-17-producing T cells in inflammatory responses

K. Hirota; J.H. Duarte; M. Veldhoen; E. Hornsby; Y. Li; H. Ahlfors; C. Wilhelm; M. Tolaini; U. Menzel; A. Garefalaki; A.J. Potocnik; B. Stockinger; D.J. Cua

doi:10.1038/ni.1993

Fate mapping of IL-17-producing T cells in inflammatory responses

K. Hirota, J.H. Duarte, M. Veldhoen, E. Hornsby, Y. Li, H. Ahlfors, C. Wilhelm, M. Tolaini, U. Menzel, A. Garefalaki, A.J. Potocnik, B. Stockinger, D.J. Cua

School of Biological Sciences

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

Abstract / Description of output

Here we describe a reporter mouse strain designed to map the fate of cells that have activated interleukin 17A (IL-17A). We found that IL-17-producing helper T cells (T 17 cells) had distinct plasticity in different inflammatory settings. Chronic inflammatory conditions in experimental autoimmune encephalomyelitis (EAE) caused a switch to alternative cytokines in T 17 cells, whereas acute cutaneous infection with Candida albicans did not result in the deviation of T 17 cells to the production of alternative cytokines, although IL-17A production was shut off in the course of the infection. During the development of EAE, interferon-γ (IFN-γ) and other proinflammatory cytokines in the spinal cord were produced almost exclusively by cells that had produced IL-17 before their conversion by IL-23 ('ex-T 17 cells'). Thus, this model allows the actual functional fate of effector T cells to be related to T 17 developmental origin regardless of IL-17 expression.

Original language	English
Pages (from-to)	255-263
Number of pages	9
Journal	Nature Immunology
Volume	12
Issue number	3
Early online date	30 Jan 2011
DOIs	https://doi.org/10.1038/ni.1993
Publication status	Published - 1 Mar 2011

Keywords / Materials (for Non-textual outputs)

cytokine
gamma interferon
interleukin 17
interleukin 23
allergic encephalomyelitis
animal cell
animal experiment
animal model
animal tissue
article
candidiasis
CD4+ T lymphocyte
cell fate
controlled study
gene mapping
genetic transcription
helper cell
in vivo study
inflammation
mouse
nonhuman
priority journal
Animals
Encephalomyelitis, Autoimmune, Experimental
Flow Cytometry
Genes, Reporter
Inflammation
Interferon-gamma
Interleukin-17
Mice
Mice, Knockout
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
T-Lymphocytes
T-helper 17 cells

Access to Document

10.1038/ni.1993Licence: All Rights Reserved

Cite this

@article{2dc38bfe24234887a5f6a00899ded1f6,

title = "Fate mapping of IL-17-producing T cells in inflammatory responses",

abstract = "Here we describe a reporter mouse strain designed to map the fate of cells that have activated interleukin 17A (IL-17A). We found that IL-17-producing helper T cells (T 17 cells) had distinct plasticity in different inflammatory settings. Chronic inflammatory conditions in experimental autoimmune encephalomyelitis (EAE) caused a switch to alternative cytokines in T 17 cells, whereas acute cutaneous infection with Candida albicans did not result in the deviation of T 17 cells to the production of alternative cytokines, although IL-17A production was shut off in the course of the infection. During the development of EAE, interferon-γ (IFN-γ) and other proinflammatory cytokines in the spinal cord were produced almost exclusively by cells that had produced IL-17 before their conversion by IL-23 ('ex-T 17 cells'). Thus, this model allows the actual functional fate of effector T cells to be related to T 17 developmental origin regardless of IL-17 expression.",

keywords = "cytokine, gamma interferon, interleukin 17, interleukin 23, allergic encephalomyelitis, animal cell, animal experiment, animal model, animal tissue, article, candidiasis, CD4+ T lymphocyte, cell fate, controlled study, gene mapping, genetic transcription, helper cell, in vivo study, inflammation, mouse, nonhuman, priority journal, Animals, Encephalomyelitis, Autoimmune, Experimental, Flow Cytometry, Genes, Reporter, Inflammation, Interferon-gamma, Interleukin-17, Mice, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, T-Lymphocytes, T-helper 17 cells",

author = "K. Hirota and J.H. Duarte and M. Veldhoen and E. Hornsby and Y. Li and H. Ahlfors and C. Wilhelm and M. Tolaini and U. Menzel and A. Garefalaki and A.J. Potocnik and B. Stockinger and D.J. Cua",

note = "Cited By :283 Export Date: 11 March 2015 CODEN: NIAMC Correspondence Address: Potocnik, A. J.; Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, United Kingdom; email: [email protected] Chemicals/CAS: gamma interferon, 82115-62-6; Interferon-gamma, 82115-62-6; Interleukin-17 References: Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M., Weaver, C.T., Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages (2005) Nature Immunology, 6 (11), pp. 1123-1132. , DOI 10.1038/ni1254, PII N1254; Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.-H., Wang, Y., Dong, C., A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 (2005) Nature Immunology, 6 (11), pp. 1133-1141. , DOI 10.1038/ni1261, PII N1261; Veldhoen, M., Hocking, R.J., Atkins, C.J., Locksley, R.M., Stockinger, B., TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells (2006) Immunity, 24 (2), pp. 179-189. , DOI 10.1016/j.immuni.2006.01.001, PII S1074761306000045; Ivanov, I.I., McKenzie, B.S., Zhou, L., Tadokoro, C.E., Lepelley, A., Lafaille, J.J., Cua, D.J., Littman, D.R., The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells (2006) Cell, 126 (6), pp. 1121-1133. , DOI 10.1016/j.cell.2006.07.035, PII S0092867406011056; Yang, X.O., T helper 17 lineage differentiation is programmed by orphan nuclear receptors RORα and RORγ (2008) Immunity, 28, pp. 29-39; Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Romagnani, S., Phenotypic and functional features of human Th17 cells (2007) Journal of Experimental Medicine, 204 (8), pp. 1849-1861. , http://www.jem.org/cgi/reprint/204/8/1849, DOI 10.1084/jem.20070663; Bending, D., Highly purifed Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice (2009) J. Clin. Invest., 119, pp. 565-572; Lee, Y.K., Late developmental plasticity in the T helper 17 lineage (2009) Immunity, 30, pp. 92-107; Martin-Orozco, N., Th17 cells promote pancreatic infammation but only induce diabetes effciently in lymphopenic hosts after conversion into Th1 cells (2009) Eur. J. Immunol., 39, pp. 216-224; Shi, G., Phenotype switching by infammation-inducing polarized Th17 cells, but not by Th1 cells (2008) J. Immunol., 181, pp. 7205-7213; Bettelli, E., Kuchroo, V.K., IL-12- and IL-23-induced T helper cell subsets: Birds of the same feather flock together (2005) Journal of Experimental Medicine, 201 (2), pp. 169-171. , DOI 10.1084/jem.20042279; Lexberg, M.H., Th memory for interleukin-17 expression is stable in vivo (2008) Eur. J. Immunol., 38, pp. 2654-2664; Hirota, K., Martin, B., Veldhoen, M., Development regulation and functional capacities of Th17 cells (2010) Semin. Immunopathol., 32, pp. 3-16; Spits, H., Di Santo, J.P., The expanding family of innate lymphoid cells: Regulators and effectors of immunity and tissue remodeling (2011) Nat Immunol., 12, pp. 21-27; Luger, D., Silver, P.B., Tang, J., Cua, D., Chen, Z., Iwakura, Y., Bowman, E.P., Caspi, R.R., Either a Th17 or a Th1 effector response can drive autoimmunity: Conditions of disease induction affect dominant effector category (2008) Journal of Experimental Medicine, 205 (4), pp. 799-810. , http://www.jem.org/cgi/reprint/205/4/799, DOI 10.1084/jem.20071258; Bettelli, E., Pagany, M., Weiner, H.L., Linington, C., Sobel, R.A., Kuchroo, V.K., Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis (2003) Journal of Experimental Medicine, 197 (9), pp. 1073-1081. , DOI 10.1084/jem.20021603; McGeachy, M.J., The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo (2009) Nat Immunol., 10, pp. 314-324; Zhou, L., Chong, M.M., Littman, D.R., Plasticity of CD4+ T cell lineage differentiation (2009) Immunity, 30, pp. 646-655; De Beaucoudrey, L., Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells (2008) J. Exp. Med., 205, pp. 1543-1550; Milner, J.D., Brenchley, J.M., Laurence, A., Freeman, A.F., Hill, B.J., Elias, K.M., Kanno, Y., Douek, D.C., Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome (2008) Nature, 452 (7188), pp. 773-776. , DOI 10.1038/nature06764, PII NATURE06764; Kisand, K., Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines (2010) J. Exp. Med., 207, pp. 299-308; O'Shea, J.J., Paul, W.E., Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells (2010) Science, 327, pp. 1098-1102; Murphy, K.M., Stockinger, B., Effector T cell plasticity: Fexibility in the fact of changing circumstances (2010) Nat Immunol., 11, pp. 674-680; Mukasa, R., Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage (2010) Immunity, 32, pp. 616-627; Wei, G., Global mapping of H3K4me3 and H3K27me3 reveals specifcity and plasticity in lineage fate determination of differentiating CD4+ T cells (2009) Immunity, 30, pp. 155-167; Croxford, A.L., Kurschus, F.C., Waisman, A., Cutting edge: An IL-17F-CreEYFP reporter mouse allows fate mapping of Th17 cells (2009) J. Immunol., 182, pp. 1237-1241; Chang, S.H., Dong, C., IL-17F: Regulation, signaling and function in infammation (2009) Cytokine, 46, pp. 7-11; Ahern, P.P., Interleukin-23 drives intestinal infammation through direct activity on T cells (2010) Immunity, 33, pp. 279-288; Veldhoen, M., Hocking, R.J., Flavell, R.A., Stockinger, B., Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease (2006) Nature Immunology, 7 (11), pp. 1151-1156. , DOI 10.1038/ni1391, PII NI1391; Ponomarev, E.D., Shriver, L.P., Maresz, K., Pedras-Vasconcelos, J., Verthelyi, D., Dittel, B.N., GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis (2007) Journal of Immunology, 178 (1), pp. 39-48; McQualter, J.L., Granulocyte macrophage colony-stimulating factor: A new putative therapeutic target in multiple sclerosis (2001) J. Exp. Med., 194, pp. 873-882; Boniface, K., Human Th17 cells comprise heterogeneous subsets including IFN-γ-producing cells with distinct properties from the Th1 lineage (2010) J. Immunol., 185, pp. 679-687; Stevens, E.A., Mezrich, J.D., Bradfeld, C.A., The aryl hydrocarbon receptor: A perspective on potential roles in the immune system (2009) Immunology, 127, pp. 299-311; Szabo, S.J., Dighe, A.S., Gubler, U., Murphy, K.M., Regulation of the interleukin (IL)-12R β2 subunit expression in developing T helper 1 (Th1) and Th2 cells (1997) Journal of Experimental Medicine, 185 (5), pp. 817-824. , DOI 10.1084/jem.185.5.817; Hegazy, A.N., Interferons direct Th2 cell reprogramming to generate a stable GATA-3+T-bet+ cell subset with combined Th2 and Th1 cell functions (2010) Immunity, 32, pp. 116-128; Bailey-Bucktrout, S.L., Cutting edge: Central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis (2008) J. Immunol., 180, pp. 6457-6461; Isaksson, M., Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE (2009) Eur. J. Immunol., 39, pp. 2925-2935; Shinohara, M.L., Kim, J.H., Garcia, V.A., Cantor, H., Engagement of the type i interferon receptor on dendritic cells inhibits T helper 17 cell development: Role of intracellular osteopontin (2008) Immunity, 29, pp. 68-78; Axtell, R.C., T helper type 1 and 17 cells determine effcacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis (2010) Nat Med., 16, pp. 406-412; Stromnes, I.M., Cerretti, L.M., Liggitt, D., Harris, R.A., Goverman, J.M., Differential regulation of central nervous system autoimmunity by T H1 and TH17 cells (2008) Nature Medicine, 14 (3), pp. 337-342. , DOI 10.1038/nm1715, PII NM1715; Lees, J.R., Regional CNS responses to IFN-γ determine lesion localization patterns during EAE pathogenesis (2008) J. Exp. Med., 205, pp. 2633-2642; Steinman, L., A rush to judgment on Th17 (2008) Journal of Experimental Medicine, 205 (7), pp. 1517-1522. , http://www.jem.org/cgi/reprint/205/7/1517, DOI 10.1084/jem.20072066; O'Connor, R.A., Cutting edge: Th1 cells facilitate the entry of Th17 cells to the central nervous system during experimental autoimmune encephalomyelitis (2008) J. Immunol., 181, pp. 3750-3754; McGeachy, M.J., Bak-Jensen, K.S., Chen, Y., Tato, C.M., Blumenschein, W., McClanahan, T., Cua, D.J., TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology (2007) Nature Immunology, 8 (12), pp. 1390-1397. , DOI 10.1038/ni1539, PII NI1539; Suryani, S., Sutton, I., An interferon-γ-producing Th1 subset is the major source of IL-17 in experimental autoimmune encephalitis (2007) Journal of Neuroimmunology, 183 (1-2), pp. 96-103. , DOI 10.1016/j.jneuroim.2006.11.023, PII S0165572806004814; McGeachy, M.J., Cua, D.J., Th17 Cell Differentiation: The Long and Winding Road (2008) Immunity, 28 (4), pp. 445-453. , DOI 10.1016/j.immuni.2008.03.001, PII S1074761308001155; Michel, M.L., Identifcation of an IL-17-producing NK1.1- iNKT cell population involved in airway neutrophilia (2007) J. Exp. Med., 204, pp. 995-1001; Ghoreschi, K., Generation of pathogenic TH17 cells in the absence of TGF-beta signalling (2010) Nature, 467, pp. 967-971; Pepper, M., Different routes of bacterial infection induce long-lived TH1 memory cells and short-lived TH17 cells (2010) Nat Immunol., 11, pp. 83-89; Sutton, C., Brereton, C., Keogh, B., Mills, K.H.G., Lavelle, E.C., A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis (2006) Journal of Experimental Medicine, 203 (7), pp. 1685-1691. , http://www.jem.org/cgi/reprint/203/7/1685, DOI 10.1084/jem.20060285; Shimshek, D.R., Kim, J., Hubner, M.R., Spergel, D.J., Buchholz, F., Casanova, E., Stewart, A.F., Sprengel, R., Codon-improved Cre recombinase (iCre) expression in the mouse (2002) Genesis, 32 (1), pp. 19-26. , DOI 10.1002/gene.10023; Srinivas, S., Cre reporter strains produced by targeted insertion of EYFP and ECFP into the ROSA26 locus (2001) BMC Dev. Biol., 1, p. 4",

year = "2011",

month = mar,

day = "1",

doi = "10.1038/ni.1993",

language = "English",

volume = "12",

pages = "255--263",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "3",

}

TY - JOUR

T1 - Fate mapping of IL-17-producing T cells in inflammatory responses

AU - Hirota, K.

AU - Duarte, J.H.

AU - Veldhoen, M.

AU - Hornsby, E.

AU - Li, Y.

AU - Ahlfors, H.

AU - Wilhelm, C.

AU - Tolaini, M.

AU - Menzel, U.

AU - Garefalaki, A.

AU - Potocnik, A.J.

AU - Stockinger, B.

AU - Cua, D.J.

N1 - Cited By :283 Export Date: 11 March 2015 CODEN: NIAMC Correspondence Address: Potocnik, A. J.; Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, United Kingdom; email: [email protected] Chemicals/CAS: gamma interferon, 82115-62-6; Interferon-gamma, 82115-62-6; Interleukin-17 References: Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M., Weaver, C.T., Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages (2005) Nature Immunology, 6 (11), pp. 1123-1132. , DOI 10.1038/ni1254, PII N1254; Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.-H., Wang, Y., Dong, C., A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 (2005) Nature Immunology, 6 (11), pp. 1133-1141. , DOI 10.1038/ni1261, PII N1261; Veldhoen, M., Hocking, R.J., Atkins, C.J., Locksley, R.M., Stockinger, B., TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells (2006) Immunity, 24 (2), pp. 179-189. , DOI 10.1016/j.immuni.2006.01.001, PII S1074761306000045; Ivanov, I.I., McKenzie, B.S., Zhou, L., Tadokoro, C.E., Lepelley, A., Lafaille, J.J., Cua, D.J., Littman, D.R., The Orphan Nuclear Receptor RORγt Directs the Differentiation Program of Proinflammatory IL-17+ T Helper Cells (2006) Cell, 126 (6), pp. 1121-1133. , DOI 10.1016/j.cell.2006.07.035, PII S0092867406011056; Yang, X.O., T helper 17 lineage differentiation is programmed by orphan nuclear receptors RORα and RORγ (2008) Immunity, 28, pp. 29-39; Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Romagnani, S., Phenotypic and functional features of human Th17 cells (2007) Journal of Experimental Medicine, 204 (8), pp. 1849-1861. , http://www.jem.org/cgi/reprint/204/8/1849, DOI 10.1084/jem.20070663; Bending, D., Highly purifed Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice (2009) J. Clin. Invest., 119, pp. 565-572; Lee, Y.K., Late developmental plasticity in the T helper 17 lineage (2009) Immunity, 30, pp. 92-107; Martin-Orozco, N., Th17 cells promote pancreatic infammation but only induce diabetes effciently in lymphopenic hosts after conversion into Th1 cells (2009) Eur. J. Immunol., 39, pp. 216-224; Shi, G., Phenotype switching by infammation-inducing polarized Th17 cells, but not by Th1 cells (2008) J. Immunol., 181, pp. 7205-7213; Bettelli, E., Kuchroo, V.K., IL-12- and IL-23-induced T helper cell subsets: Birds of the same feather flock together (2005) Journal of Experimental Medicine, 201 (2), pp. 169-171. , DOI 10.1084/jem.20042279; Lexberg, M.H., Th memory for interleukin-17 expression is stable in vivo (2008) Eur. J. Immunol., 38, pp. 2654-2664; Hirota, K., Martin, B., Veldhoen, M., Development regulation and functional capacities of Th17 cells (2010) Semin. Immunopathol., 32, pp. 3-16; Spits, H., Di Santo, J.P., The expanding family of innate lymphoid cells: Regulators and effectors of immunity and tissue remodeling (2011) Nat Immunol., 12, pp. 21-27; Luger, D., Silver, P.B., Tang, J., Cua, D., Chen, Z., Iwakura, Y., Bowman, E.P., Caspi, R.R., Either a Th17 or a Th1 effector response can drive autoimmunity: Conditions of disease induction affect dominant effector category (2008) Journal of Experimental Medicine, 205 (4), pp. 799-810. , http://www.jem.org/cgi/reprint/205/4/799, DOI 10.1084/jem.20071258; Bettelli, E., Pagany, M., Weiner, H.L., Linington, C., Sobel, R.A., Kuchroo, V.K., Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis (2003) Journal of Experimental Medicine, 197 (9), pp. 1073-1081. , DOI 10.1084/jem.20021603; McGeachy, M.J., The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo (2009) Nat Immunol., 10, pp. 314-324; Zhou, L., Chong, M.M., Littman, D.R., Plasticity of CD4+ T cell lineage differentiation (2009) Immunity, 30, pp. 646-655; De Beaucoudrey, L., Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells (2008) J. Exp. Med., 205, pp. 1543-1550; Milner, J.D., Brenchley, J.M., Laurence, A., Freeman, A.F., Hill, B.J., Elias, K.M., Kanno, Y., Douek, D.C., Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome (2008) Nature, 452 (7188), pp. 773-776. , DOI 10.1038/nature06764, PII NATURE06764; Kisand, K., Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines (2010) J. Exp. Med., 207, pp. 299-308; O'Shea, J.J., Paul, W.E., Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells (2010) Science, 327, pp. 1098-1102; Murphy, K.M., Stockinger, B., Effector T cell plasticity: Fexibility in the fact of changing circumstances (2010) Nat Immunol., 11, pp. 674-680; Mukasa, R., Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage (2010) Immunity, 32, pp. 616-627; Wei, G., Global mapping of H3K4me3 and H3K27me3 reveals specifcity and plasticity in lineage fate determination of differentiating CD4+ T cells (2009) Immunity, 30, pp. 155-167; Croxford, A.L., Kurschus, F.C., Waisman, A., Cutting edge: An IL-17F-CreEYFP reporter mouse allows fate mapping of Th17 cells (2009) J. Immunol., 182, pp. 1237-1241; Chang, S.H., Dong, C., IL-17F: Regulation, signaling and function in infammation (2009) Cytokine, 46, pp. 7-11; Ahern, P.P., Interleukin-23 drives intestinal infammation through direct activity on T cells (2010) Immunity, 33, pp. 279-288; Veldhoen, M., Hocking, R.J., Flavell, R.A., Stockinger, B., Signals mediated by transforming growth factor-β initiate autoimmune encephalomyelitis, but chronic inflammation is needed to sustain disease (2006) Nature Immunology, 7 (11), pp. 1151-1156. , DOI 10.1038/ni1391, PII NI1391; Ponomarev, E.D., Shriver, L.P., Maresz, K., Pedras-Vasconcelos, J., Verthelyi, D., Dittel, B.N., GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis (2007) Journal of Immunology, 178 (1), pp. 39-48; McQualter, J.L., Granulocyte macrophage colony-stimulating factor: A new putative therapeutic target in multiple sclerosis (2001) J. Exp. Med., 194, pp. 873-882; Boniface, K., Human Th17 cells comprise heterogeneous subsets including IFN-γ-producing cells with distinct properties from the Th1 lineage (2010) J. Immunol., 185, pp. 679-687; Stevens, E.A., Mezrich, J.D., Bradfeld, C.A., The aryl hydrocarbon receptor: A perspective on potential roles in the immune system (2009) Immunology, 127, pp. 299-311; Szabo, S.J., Dighe, A.S., Gubler, U., Murphy, K.M., Regulation of the interleukin (IL)-12R β2 subunit expression in developing T helper 1 (Th1) and Th2 cells (1997) Journal of Experimental Medicine, 185 (5), pp. 817-824. , DOI 10.1084/jem.185.5.817; Hegazy, A.N., Interferons direct Th2 cell reprogramming to generate a stable GATA-3+T-bet+ cell subset with combined Th2 and Th1 cell functions (2010) Immunity, 32, pp. 116-128; Bailey-Bucktrout, S.L., Cutting edge: Central nervous system plasmacytoid dendritic cells regulate the severity of relapsing experimental autoimmune encephalomyelitis (2008) J. Immunol., 180, pp. 6457-6461; Isaksson, M., Plasmacytoid DC promote priming of autoimmune Th17 cells and EAE (2009) Eur. J. Immunol., 39, pp. 2925-2935; Shinohara, M.L., Kim, J.H., Garcia, V.A., Cantor, H., Engagement of the type i interferon receptor on dendritic cells inhibits T helper 17 cell development: Role of intracellular osteopontin (2008) Immunity, 29, pp. 68-78; Axtell, R.C., T helper type 1 and 17 cells determine effcacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis (2010) Nat Med., 16, pp. 406-412; Stromnes, I.M., Cerretti, L.M., Liggitt, D., Harris, R.A., Goverman, J.M., Differential regulation of central nervous system autoimmunity by T H1 and TH17 cells (2008) Nature Medicine, 14 (3), pp. 337-342. , DOI 10.1038/nm1715, PII NM1715; Lees, J.R., Regional CNS responses to IFN-γ determine lesion localization patterns during EAE pathogenesis (2008) J. Exp. Med., 205, pp. 2633-2642; Steinman, L., A rush to judgment on Th17 (2008) Journal of Experimental Medicine, 205 (7), pp. 1517-1522. , http://www.jem.org/cgi/reprint/205/7/1517, DOI 10.1084/jem.20072066; O'Connor, R.A., Cutting edge: Th1 cells facilitate the entry of Th17 cells to the central nervous system during experimental autoimmune encephalomyelitis (2008) J. Immunol., 181, pp. 3750-3754; McGeachy, M.J., Bak-Jensen, K.S., Chen, Y., Tato, C.M., Blumenschein, W., McClanahan, T., Cua, D.J., TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology (2007) Nature Immunology, 8 (12), pp. 1390-1397. , DOI 10.1038/ni1539, PII NI1539; Suryani, S., Sutton, I., An interferon-γ-producing Th1 subset is the major source of IL-17 in experimental autoimmune encephalitis (2007) Journal of Neuroimmunology, 183 (1-2), pp. 96-103. , DOI 10.1016/j.jneuroim.2006.11.023, PII S0165572806004814; McGeachy, M.J., Cua, D.J., Th17 Cell Differentiation: The Long and Winding Road (2008) Immunity, 28 (4), pp. 445-453. , DOI 10.1016/j.immuni.2008.03.001, PII S1074761308001155; Michel, M.L., Identifcation of an IL-17-producing NK1.1- iNKT cell population involved in airway neutrophilia (2007) J. Exp. 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PY - 2011/3/1

Y1 - 2011/3/1

N2 - Here we describe a reporter mouse strain designed to map the fate of cells that have activated interleukin 17A (IL-17A). We found that IL-17-producing helper T cells (T 17 cells) had distinct plasticity in different inflammatory settings. Chronic inflammatory conditions in experimental autoimmune encephalomyelitis (EAE) caused a switch to alternative cytokines in T 17 cells, whereas acute cutaneous infection with Candida albicans did not result in the deviation of T 17 cells to the production of alternative cytokines, although IL-17A production was shut off in the course of the infection. During the development of EAE, interferon-γ (IFN-γ) and other proinflammatory cytokines in the spinal cord were produced almost exclusively by cells that had produced IL-17 before their conversion by IL-23 ('ex-T 17 cells'). Thus, this model allows the actual functional fate of effector T cells to be related to T 17 developmental origin regardless of IL-17 expression.

AB - Here we describe a reporter mouse strain designed to map the fate of cells that have activated interleukin 17A (IL-17A). We found that IL-17-producing helper T cells (T 17 cells) had distinct plasticity in different inflammatory settings. Chronic inflammatory conditions in experimental autoimmune encephalomyelitis (EAE) caused a switch to alternative cytokines in T 17 cells, whereas acute cutaneous infection with Candida albicans did not result in the deviation of T 17 cells to the production of alternative cytokines, although IL-17A production was shut off in the course of the infection. During the development of EAE, interferon-γ (IFN-γ) and other proinflammatory cytokines in the spinal cord were produced almost exclusively by cells that had produced IL-17 before their conversion by IL-23 ('ex-T 17 cells'). Thus, this model allows the actual functional fate of effector T cells to be related to T 17 developmental origin regardless of IL-17 expression.

KW - cytokine

KW - gamma interferon

KW - interleukin 17

KW - interleukin 23

KW - allergic encephalomyelitis

KW - animal cell

KW - animal experiment

KW - animal model

KW - animal tissue

KW - article

KW - candidiasis

KW - CD4+ T lymphocyte

KW - cell fate

KW - controlled study

KW - gene mapping

KW - genetic transcription

KW - helper cell

KW - in vivo study

KW - inflammation

KW - mouse

KW - nonhuman

KW - priority journal

KW - Animals

KW - Encephalomyelitis, Autoimmune, Experimental

KW - Flow Cytometry

KW - Genes, Reporter

KW - Inflammation

KW - Interferon-gamma

KW - Interleukin-17

KW - Mice

KW - Mice, Knockout

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Signal Transduction

KW - T-Lymphocytes

KW - T-helper 17 cells

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-79951677394&partnerID=8YFLogxK

U2 - 10.1038/ni.1993

DO - 10.1038/ni.1993

M3 - Article

AN - SCOPUS:79951677394

SN - 1529-2908

VL - 12

SP - 255

EP - 263

JO - Nature Immunology

JF - Nature Immunology

IS - 3

ER -

Fate mapping of IL-17-producing T cells in inflammatory responses

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