KEGG PATHWAY: map04657

PATHWAY: map04657

Entry

map04657                    Pathway

Name

IL-17 signaling pathway

Description

The interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A-F, plays crucial roles in both acute and chronic inflammatory responses. IL-17A, the hallmark cytokine of the newly defined T helper 17 (TH17) cell subset, has important roles in protecting the host against extracellular pathogens, but also promotes inflammatory pathology in autoimmune disease, whereas IL-17F is mainly involved in mucosal host defense mechanisms. IL-17E (IL-25) is an amplifier of Th2 immune responses. IL-17C has biological functions similar to those of IL-17A. The functions of IL-17B and IL-17D remain largely elusive. The IL-17 family signals via their correspondent receptors and activates downstream pathways that include NF-kappaB, MAPKs and C/EBPs to induce the expression of antimicrobial peptides, cytokines and chemokines. The receptor proximal adaptor Act1 (an NF-kappaB activator 1) is considered as the master mediator in IL-17A signaling. It is likely that Act1 is a common signal adaptor also shared by other members mediated signalings in this family.

Class

Organismal Systems; Immune system

Pathway map

map04657

IL-17 signaling pathway

Other DBs

GO:

0097400

Reference

PMID:23917206

Authors

Song X, Qian Y

Title

IL-17 family cytokines mediated signaling in the pathogenesis of inflammatory diseases.

Journal

Cell Signal 25:2335-47 (2013)
DOI:10.1016/j.cellsig.2013.07.021

Reference

PMID:23557798

Authors

Song X, Qian Y

Title

The activation and regulation of IL-17 receptor mediated signaling.

Journal

Cytokine 62:175-82 (2013)
DOI:10.1016/j.cyto.2013.03.014

Reference

PMID:24011563

Authors

Gu C, Wu L, Li X

Title

IL-17 family: cytokines, receptors and signaling.

Journal

Cytokine 64:477-85 (2013)
DOI:10.1016/j.cyto.2013.07.022

Reference

PMID:25145755

Authors

Gaffen SL, Jain R, Garg AV, Cua DJ

Title

The IL-23-IL-17 immune axis: from mechanisms to therapeutic testing.

Journal

Nat Rev Immunol 14:585-600 (2014)
DOI:10.1038/nri3707

Reference

PMID:21349428

Authors

Iwakura Y, Ishigame H, Saijo S, Nakae S

Title

Functional specialization of interleukin-17 family members.

Journal

Immunity 34:149-62 (2011)
DOI:10.1016/j.immuni.2011.02.012

Reference

PMID:20514051

Authors

Qian Y, Kang Z, Liu C, Li X

Title

IL-17 signaling in host defense and inflammatory diseases.

Journal

Cell Mol Immunol 7:328-33 (2010)
DOI:10.1038/cmi.2010.27

Reference

PMID:22324470

Authors

Zhu S, Qian Y

Title

IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential.

Journal

Clin Sci (Lond) 122:487-511 (2012)
DOI:10.1042/CS20110496

Reference

PMID:26252407

Authors

Zenobia C, Hajishengallis G

Title

Basic biology and role of interleukin-17 in immunity and inflammation.

Journal

Periodontol 2000 69:142-59 (2015)
DOI:10.1111/prd.12083

Reference

PMID:21074482

Authors

Reynolds JM, Angkasekwinai P, Dong C

Title

IL-17 family member cytokines: regulation and function in innate immunity.

Journal

Cytokine Growth Factor Rev 21:413-23 (2010)
DOI:10.1016/j.cytogfr.2010.10.002

Reference

PMID:21852080

Authors

Gaffen SL

Title

Recent advances in the IL-17 cytokine family.

Journal

Curr Opin Immunol 23:613-9 (2011)
DOI:10.1016/j.coi.2011.07.006

Reference

PMID:18701318

Authors

Gaffen SL

Title

An overview of IL-17 function and signaling.

Journal

Cytokine 43:402-7 (2008)
DOI:10.1016/j.cyto.2008.07.017

Reference

PMID:21155836

Authors

Hu Y, Shen F, Crellin NK, Ouyang W

Title

The IL-17 pathway as a major therapeutic target in autoimmune diseases.

Journal

Ann N Y Acad Sci 1217:60-76 (2011)
DOI:10.1111/j.1749-6632.2010.05825.x

Reference

PMID:20383173

Authors

Xu S, Cao X

Title

Interleukin-17 and its expanding biological functions.

Journal

Cell Mol Immunol 7:164-74 (2010)
DOI:10.1038/cmi.2010.21

Reference

PMID:20177959

Authors

Pappu R, Ramirez-Carrozzi V, Ota N, Ouyang W, Hu Y

Title

The IL-17 family cytokines in immunity and disease.

Journal

J Clin Immunol 30:185-95 (2010)
DOI:10.1007/s10875-010-9369-6

Reference

PMID:19575028

Authors

Gaffen SL

Title

Structure and signalling in the IL-17 receptor family.

Journal

Nat Rev Immunol 9:556-67 (2009)
DOI:10.1038/nri2586

Reference

PMID:18178098

Authors

Shen F, Gaffen SL

Title

Structure-function relationships in the IL-17 receptor: implications for signal transduction and therapy.

Journal

Cytokine 41:92-104 (2008)
DOI:10.1016/j.cyto.2007.11.013

Reference

PMID:23116200

Authors

Doyle MS, Collins ES, FitzGerald OM, Pennington SR

Title

New insight into the functions of the interleukin-17 receptor adaptor protein Act1 in psoriatic arthritis.

Journal

Arthritis Res Ther 14:226 (2012)
DOI:10.1186/ar4071

Reference

PMID:17027518

Authors

Gaffen SL, Kramer JM, Yu JJ, Shen F

Title

The IL-17 cytokine family.

Journal

Vitam Horm 74:255-82 (2006)
DOI:10.1016/S0083-6729(06)74010-9

Reference

PMID:21130872

Authors

Chang SH, Dong C

Title

Signaling of interleukin-17 family cytokines in immunity and inflammation.

Journal

Cell Signal 23:1069-75 (2011)
DOI:10.1016/j.cellsig.2010.11.022

Reference

PMID:17921324

Authors

Cortez DM, Feldman MD, Mummidi S, Valente AJ, Steffensen B, Vincenti M, Barnes JL, Chandrasekar B

Title

IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta , NF-kappaB, and AP-1 activation.

Journal

Am J Physiol Heart Circ Physiol 293:H3356-65 (2007)
DOI:10.1152/ajpheart.00928.2007

Reference

PMID:22851696

Authors

Qu F, Gao H, Zhu S, Shi P, Zhang Y, Liu Y, Jallal B, Yao Y, Shi Y, Qian Y

Title

TRAF6-dependent Act1 phosphorylation by the IkappaB kinase-related kinases suppresses interleukin-17-induced NF-kappaB activation.

Journal

Mol Cell Biol 32:3925-37 (2012)
DOI:10.1128/MCB.00268-12

Reference

PMID:17177681

Authors

Sharkhuu T, Matthaei KI, Forbes E, Mahalingam S, Hogan SP, Hansbro PM, Foster PS

Title

Mechanism of interleukin-25 (IL-17E)-induced pulmonary inflammation and airways hyper-reactivity.

Journal

Clin Exp Allergy 36:1575-83 (2006)
DOI:10.1111/j.1365-2222.2006.02595.x

Related
pathway

map04010

MAPK signaling pathway

map04060

Cytokine-cytokine receptor interaction

map04064

NF-kappa B signaling pathway

map04210

Apoptosis

map04659

Th17 cell differentiation

KO pathway

ko04657

All links

Gene (210562)   
   KEGG ORTHOLOGY (80)   
   RefGene (210482)   
Literature (22)   
   PubMed (22)   
All databases (210584)   

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