Structure and signalling in the IL-17 receptor family - Nature Reviews Immunology
- ️Gaffen, Sarah L.
- ️Fri Jul 03 2009
Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A. & Coffman, R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol. 136, 2348–2357 (1986).
Gor, D. O., Rose, N. R. & Greenspan, N. S. TH1–TH2: a procrustean paradigm. Nature Immunol. 4, 503–505 (2003).
Steinman, L. A brief history of TH17, the first major revision in the T H1/TH2 hypothesis of T cell-mediated tissue damage. Nature Med. 13, 139–145 (2007). This review article outlines the history of discrepancies in the T H 1–T H 2 cell paradigm, presented as a 'cautionary tale' of the process of scientific inquiry.
Oppmann, B. et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13, 715–725 (2000).
Aggarwal, S., Ghilardi, N., Xie, M. H., De Sauvage, F. J. & Gurney, A. L. Interleukin 23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin 17. J. Biol. Chem. 3, 1910–1914 (2002).
Infante-Duarte, C., Horton, H. F., Byrne, M. C. & Kamradt, T. Microbial lipopeptides induce the production of IL-17 in Th cells. J. Immunol. 165, 6107–6115 (2000).
Cua, D. J. et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421, 744–748 (2003).
Ghilardi, N. & Ouyang, W. Targeting the development and effector functions of Th17 cells. Semin. Immunol. 19, 383–393 (2007).
O'Quinn, D., Palmer, M., Lee, Y. & Weaver, C. Emergence of the Th17 pathway and its role in host defense. Adv. Immunol. 99, 115–163 (2008).
McGeachy, M. J. & Cua, D. J. Th17 cell differentiation: the long and winding road. Immunity 28, 445–453 (2008).
Yu, J. & Gaffen, S. L. Interleukin-17: a novel inflammatory cytokine that bridges innate and adaptive immunity. Front. Biosci. 13, 170–177 (2008).
Rouvier, E., Luciani, M.-F., Mattei, M.-G., Denizot, F. & Golstein, P. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J. Immunol. 150, 5445–5456 (1993).
Yao, Z. et al. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity 3, 811–821 (1995). This report describes the cloning of the first IL-17R family member, and is the first to show a role for NF-κB in IL-17-induced signal transduction.
Fossiez, F. et al. T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J. Exp. Med. 183, 2593–2603 (1996).
Hymowitz, S. G. et al. IL-17s adopt a cystine knot fold: structure and activity of a novel cytokine, IL-17F, and implications for receptor binding. Embo J. 20, 5332–5341 (2001).
Tsutsui, S., Nakamura, O. & Watanabe, T. Lamprey (Lethenteron japonicum) IL-17 upregulated by LPS-stimulation in the skin cells. Immunogenetics 59, 873–882 (2007).
Wright, J. F. et al. Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells. J. Biol. Chem. 282, 13447–13455 (2007).
Chang, S. H. & Dong, C. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res. 17, 435–440 (2007).
Yang, X. O. et al. Regulation of inflammatory responses by IL-17F. J. Exp. Med. 205, 1063–1075 (2008).
Wright, J. F. et al. The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex. J. Immunol. 181, 2799–2805 (2008).
Kuestner, R. et al. Identification of the IL-17 receptor related molecule, IL-17RC, as the receptor for IL-17F. J. Immunol. 179, 5462–5473 (2007). This report shows that IL-17RC binds with high affinity to IL-17F. This is also the first functional analysis of different splice forms of any IL-17R family member.
Ishigame, H. et al. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30, 108–119 (2009). This report is the first to directly compare Il17a−/− and Il17f−/− mice and to show that these cytokines have markedly different functions in vivo.
Gaffen, S. L., Kramer, J. M., Yu, J. J. & Shen, F. in Vitamins and Hormones Vol. 74. (ed. G. Litwack) 255–282 (Academic, London, 2006).
McAllister, F. et al. Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-α and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J. Immunol. 175, 404–412 (2005).
Dong, C. Regulation and pro-inflammatory function of interleukin-17 family cytokines. Immunol. Rev. 226, 80–86 (2008).
Claudio, E. et al. The adaptor protein CIKS/Act1 is essential for IL-25-mediated allergic airway inflammation. J. Immunol. 182, 1617–1630 (2009).
Rickel, E. A. et al. Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities. J. Immunol. 181, 4299–4310 (2008). This is the first report indicating that IL-17RA functions as a shared receptor signalling subunit for IL-17E and is required for its function in vivo .
Shi, Y. et al. A novel cytokine receptor–ligand pair. Identification, molecular characterization, and in vivo immunomodulatory activity. J. Biol. Chem. 275, 19167–19176 (2000).
Yamaguchi, Y. et al. IL-17B and IL-17C are associated with TNF-α production and contribute to the exacerbation of inflammatory arthritis. J. Immunol. 179, 7128–7136 (2007).
Hurst, S. D. et al. New IL-17 family members promote Th1 or Th2 responses in the lung: in vivo function of the novel cytokine IL-25. J. Immunol. 169, 443–453 (2002).
Li, H. et al. Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 family. Proc. Natl Acad. Sci. USA 97, 773–778 (2000).
Starnes, T. et al. Cutting edge: IL-17F, a novel cytokine selectively expressed in activated T cells and monocytes, regulates angiogenesis and endothelial cell cytokine production. J. Immunol. 167, 4137–4140 (2001).
Aggarwal, S. & Gurney, A. L. IL-17: a prototype member of an emerging family. J. Leukoc. Biol. 71, 1–8 (2002).
Yao, Z. et al. Cutting edge: human IL-17: a novel cytokine derived from T cells. J. Immunol. 155, 5483–5486 (1995).
Toy, D. et al. Cutting edge: interleukin-17 signals through a heteromeric receptor complex. J. Immunol. 177, 36–39 (2006). This report is the first to show that IL-17RC is required for IL-17A-mediated signalling.
Rong, Z. et al. IL-17RD (Sef or IL-17RLM) interacts with IL-17 receptor and mediates IL-17 signaling. Cell Res. 19, 208–215 (2008).
Ozaki, K. & Leonard, W. J. Cytokine and cytokine receptor pleiotropy and redundancy. J. Biol. Chem. 277, 29355–29358 (2002).
Shen, F. & Gaffen, S. L. Structure–function relationships in the IL-17 receptor: implications for signal transduction and therapy. Cytokine 41, 92–104 (2008).
Hsu, H. C. et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nature Immunol. 9, 166–175 (2008).
Zeng, R. et al. Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function. J. Exp. Med. 201, 139–148 (2005).
Lindemann, M. J., Hu, Z., Benczik, M., Liu, K. D. & Gaffen, S. L. Differential regulation of the IL-17 receptor by γ-c cytokines: inhibitory signaling by the phosphatidylinositol 3-kinase pathway. J. Biol. Chem. 283, 14100–14108 (2008).
Shen, F., Hu, Z., Goswami, J. & Gaffen, S. L. Identification of common transcriptional regulatory elements in interleukin-17 target genes. J. Biol. Chem. 281, 24138–24148 (2006).
Maitra, A. et al. Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression. Proc. Natl Acad. Sci USA 104, 7506–7511 (2007). This is the first detailed mutagenesis study of IL-17RA; it reveals a functional role for the SEFIR domain and includes the first description of the TILL domain and CBAD, which seem to be unique to IL-17RA.
Chan, F. K. Three is better than one: pre-ligand receptor assembly in the regulation of TNF receptor signaling. Cytokine 37, 101–107 (2007).
Kramer, J. et al. Cutting edge: identification of the pre-ligand assembly domain (PLAD) and ligand binding site in the IL-17 receptor. J. Immunol. 179, 6379–6383 (2007).
Kramer, J. et al. Cutting edge: evidence for ligand-independent multimerization of the IL-17 receptor. J. Immunol. 176, 711–715 (2006).
Kramer, J. & Gaffen, S. Interleukin-17: a new paradigm in inflammation, autoimmunity and therapy. J. Periodontol. 78, 1083–1093 (2007).
You, Z. et al. Interleukin-17 receptor-like gene is a novel antiapoptotic gene highly expressed in androgen-independent prostate cancer. Cancer Res. 66, 175–183 (2006).
Remy, I., Wilson, I. A. & Michnick, S. W. Erythropietin receptor activation by a ligand-induced conformation change. Science 283, 990–993 (1999).
Deng, G. M., Zheng, L., Chan, F. K. & Lenardo, M. Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptors. Nature Med. 11, 1066–1072 (2005).
Shen, F., Ruddy, M. J., Plamondon, P. & Gaffen, S. L. Cytokines link osteoblasts and inflammation: microarray analysis of interleukin-17- and TNF-α-induced genes in bone cells. J. Leukoc. Biol. 77, 388–399 (2005).
Park, H. et al. A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nature Immunol. 6, 1133–1141 (2005).
Ruddy, M. J. et al. Functional cooperation between interleukin-17 and tumor necrosis factor-α is mediated by CCAAT/enhancer binding protein family members. J. Biol. Chem. 279, 2559–2567 (2004). This is the first paper to show a role for C/EBP proteins in IL-17-induced signalling.
Awane, M., Andres, P. G., Li, D. J. & Reinecker, H. C. NF-κB-inducing kinase is a common mediator of IL-17-, TNF-α-, and IL-1 β-induced chemokine promoter activation in intestinal epithelial cells. J. Immunol. 162, 5337–5344 (1999).
Yamazaki, S., Muta, T., Matsuo, S. & Takeshige, K. Stimulus-specific induction of a novel nuclear factor-κB regulator, IκB-ζ, via Toll/Interleukin-1 receptor is mediated by mRNA stabilization. J. Biol. Chem. 280, 1678–1687 (2005).
Blonska, M. & Lin, X. CARMA1-mediated NF-κB and JNK activation in lymphocytes. Immunol. Rev. 228, 199–211 (2009).
Schwandner, R., Yamaguchi, K. & Cao, Z. Requirement of tumor necrosis factor-associated factor (TRAF)6 in interleukin 17 signal transduction. J. Exp. Med. 191, 1233–1239 (2000).
Chang, S. H., Park, H. & Dong, C. Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J. Biol. Chem. 281, 35603–35607 (2006).
Novatchkova, M., Leibbrandt, A., Werzowa, J., Neubuser, A. & Eisenhaber, F. The STIR-domain superfamily in signal transduction, development and immunity. Trends Biochem. Sci. 28, 226–229 (2003). This is a groundbreaking bioinformatic analysis describing the SEFIR domain, a motif that is found in members of the IL-17R family and in ACT1 and that is homologous to TIR domains.
Toshchakov, V. & Vogel, S. Cell-penetrating TIR BB loop decoy peptides: A novel class of TLR signaling inhibitors and a tool to study topology of TIR–TIR interactions. Expt. Op. Biol. Ther. 7, 1035–1050 (2007).
Shen, F. et al. IL-17 receptor signaling inhibits C/EBPβ by sequential phosphorylation of the regulatory 2 domain. Sci. Signal. 2, ra8 (2009).
Linden, A. A role for the cytoplasmic adaptor proteins Act1 in mediating IL-17 signaling. Sci. STKE 2007, re4 (2007).
Qian, Y. et al. The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nature Immunol. 8, 247–256 (2007). This study, together with reference 58, is the first to show that ACT1 binds to IL-17RA and is required for downstream signalling.
Wolf, K., Plano, G. V. & Fields, K. A. A protein secreted by the respiratory pathogen Chlamydia pneumoniae impairs IL-17 signaling via interaction with human Act1. Cell. Microbiol. 11, 769–779 (2009).
Anderson, P. Post-transcriptional control of cytokine production. Nature Immunol. 9, 353–359 (2008).
Hartupee, J. et al. IL-17 signaling for mRNA stabilization does not require TNF receptor-associated factor 6. J. Immunol. 182, 1660–1666 (2009).
Matsushita, K. et al. Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature 458, 1185–1190 (2009).
Litvak, V. et al. Function of C/EBPδ in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals. Nature Immunol. 10, 437–443 (2009).
Ramji, D. P. & Foka, P. CCAAT/enhancer-binding proteins: structure, function and regulation. Biochem. J. 365, 561–575 (2002).
Tang, Q. Q. et al. Sequential phosphorylation of CCAAT enhancer-binding protein β by MAPK and glycogen synthase kinase 3β is required for adipogenesis. Proc. Natl Acad. Sci. USA 102, 9766–9771 (2005).
Miossec, P. Interleukin-17 in rheumatoid arthritis: if T cells were to contribute to inflammation and destruction through synergy. Arthritis Rheum. 48, 594–601 (2003).
Hartupee, J., Liu, C., Novotny, M., Li, X. & Hamilton, T. IL-17 enhances chemokine gene expression through mRNA stabilization. J. Immunol. 179, 4135–4141 (2007).
Huang, F. et al. Requirement for both JAK-mediated PI3K signaling and ACT1/TRAF6/TAK1-dependent NF-κB activation by IL-17A in enhancing cytokine expression in human airway epithelial cells. J. Immunol. 179, 6504–6513 (2007).
Kim, K. W. et al. Increased interleukin-17 production via a phosphoinositide 3-kinase/Akt and nuclear factor κB-dependent pathway in patients with rheumatoid arthritis. Arthritis Res. Ther. 7, R139–R148 (2005).
Rong, Z. et al. Interleukin-17F signaling requires ubiquitination of interleukin-17 receptor via TRAF6. Cell Signal. 19, 1514–1520 (2007).
Zheng, Y. et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nature Med. 14, 282–289 (2008).
Haudenschild, D., Moseley, T., Rose, L. & Reddi, A. H. Soluble and transmembrane isoforms of novel interleukin-17 receptor-like protein by RNA splicing and expression in prostate cancer. J. Biol. Chem. 277, 4309–4316 (2002).
Haudenschild, D. R., Curtiss, S. B., Moseley, T. A. & Reddi, A. H. Generation of interleukin-17 receptor-like protein (IL-17RL) in prostate by alternative splicing of RNA. Prostate 66, 1268–1274 (2006).
Lee, J. et al. IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1. J. Biol. Chem. 276, 1660–1664 (2001).
Moseley, T. A., Haudenschild, D. R., Rose, L. & Reddi, A. H. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 14, 155–174 (2003).
Maezawa, Y. et al. Involvement of TNF receptor-associated factor 6 in IL-25 receptor signaling. J. Immunol. 176, 1013–1018 (2006).
Angkasekwinai, P. et al. Interleukin 25 promotes the initiation of proallergic type 2 responses. J. Exp. Med. 204, 1509–1517 (2007).
Swaidani, S. et al. The critical role of epithelial-derived Act1 in IL-17- and IL-25-mediated pulmonary inflammation. J. Immunol. 182, 1631–1640 (2009).
Pancer, Z., Mayer, W. E., Klein, J. & Cooper, M. D. Prototypic T cell receptor and CD4-like coreceptor are expressed by lymphocytes in the agnathan sea lamprey. Proc. Natl Acad. Sci USA 101, 13273–13278 (2004).
Tsang, M., Friesel, R., Kudoh, T. & Dawid, I. Identification of Sef, a novel modulator of FGF signalling. Nature Cell Biol. 4, 165–169 (2002).
Yang, R. B. et al. A novel interleukin-17 receptor-like protein identified in human umbilical vein endothelial cells antagonizes basic fibroblast growth factor-induced signaling. J. Biol. Chem. 278, 33232–33238 (2003).
Xiong, S. et al. hSef inhibits PC-12 cell differentiation by interfering with Ras–mitogen-activated protein kinase MAPK signaling. J. Biol. Chem. 278, 50273–50282 (2003).
Preger, E. et al. Alternative splicing generates an isoform of the human Sef gene with altered subcellular localization and specificity. Proc. Natl Acad. Sci. USA 101, 1229–1234 (2004).
Yang, X. et al. Sef interacts with TAK1 and mediates JNK activation and apoptosis. J. Biol. Chem. 279, 38099–38102 (2004).
Li, T. S., Li, X. N., Chang, Z. J., Fu, X. Y. & Liu, L. Identification and functional characterization of a novel interleukin 17 receptor: a possible mitogenic activation through ras/mitogen-activated protein kinase signaling pathway. Cell Signal. 18, 1287–1298 (2006).
McInnes, I. B. & Schett, G. Cytokines in the pathogenesis of rheumatoid arthritis. Nature Rev. Immunol. 7, 429–442 (2007).
Kikly, K., Liu, L., Na, S. & Sedgwick, J. D. The IL-23/Th17 axis: therapeutic targets for autoimmune inflammation. Curr. Opin. Immunol. 18, 670–675 (2006).
Lubberts, E. IL-17/Th17 targeting: on the road to prevent chronic destructive arthritis? Cytokine 41, 84–91 (2008).
Ye, P. et al. Requirement of interleukin 17 receptor signaling for lung CXC chemokine and granulocyte colony-stimulating factor expression, neutrophil recruitment, and host defense. J. Exp. Med 194, 519–527 (2001).
Chabaud, M., Lubberts, E., Joosten, L., van Den Berg, W. & Miossec, P. IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis. Arthritis Res. 3, 168–177 (2001).
Lubberts, E. et al. IL-1-independent role of IL-17 in synovial inflammation and joint destruction during collagen-induced arthritis. J. Immunol. 167, 1004–1013 (2001).
Murphy, C. A. et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J. Exp. Med 198, 1951–1957 (2003).
Harrington, L. E. et al. Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nature Immunol. 6, 1123–1132 (2005).
Langrish, C. L. et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med 201, 233–240 (2005).
Duerr, R. H. et al. A Genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314, 1461–1463 (2006).
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. Immunity 24, 179–189 (2006).
Mangan, P. R. et al. Transforming growth factor-β induces development of the T H17 lineage. Nature 441, 231–234 (2006).
Bettelli, E. et al. Reciprocal developmental pathways for the generation of pathogenic effector T H17 and regulatory T cells. Nature 441, 235–238 (2006).
Ivanov, I. et al. The orphan nuclear receptor RORγT directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121–1133 (2006).
Liang, S. C. et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med 203, 2271–2279 (2006).
Korn, T. et al. IL-21 initiates an alternative pathway to induce proinflammatory TH17 cells. Nature 448, 484–487 (2007).
Nurieva, R. et al. Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448, 480–483 (2007).
Zhou, L. et al. IL-6 programs T H-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nature Immunol. 8, 967–974 (2007).
Milner, J. D. et al. Impaired T H17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452, 773–776 (2008).