KEGG PATHWAY: ko04657

PATHWAY: ko04657

Entry

ko04657                     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

ko04657

IL-17 signaling pathway

Other DBs

GO:

0097400

Orthology

K01388

MMP1; matrix metalloproteinase-1 (interstitial collagenase) [EC:3.4.24.7]

K01394

MMP3; matrix metalloproteinase-3 (stromelysin 1, progelatinase) [EC:3.4.24.17]

K01403

MMP9; matrix metalloproteinase-9 (gelatinase B) [EC:3.4.24.35]

K02187

CASP3; caspase 3 [EC:3.4.22.56]

K02373

FADD; FAS-associated death domain protein

K02580

NFKB1; nuclear factor NF-kappa-B p105 subunit

K03083

GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]

K03156

TNF, TNFA; tumor necrosis factor superfamily, member 2

K03171

TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein

K03173

TRAF2; TNF receptor-associated factor 2 [EC:2.3.2.27]

K03174

TRAF3; TNF receptor-associated factor 3

K03175

TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]

K03352

APC5, ANAPC5; anaphase-promoting complex subunit 5

K04079

HSP90A, htpG; molecular chaperone HtpG

K04371

ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K04379

FOS; proto-oncogene protein c-fos

K04398

CASP8; caspase 8 [EC:3.4.22.61]

K04404

MAP3K7IP2, TAB2; TAK1-binding protein 2

K04427

MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25]

K04440

JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]

K04441

P38; p38 MAP kinase [EC:2.7.11.24]

K04448

JUN; transcription factor AP-1

K04449

JUND; transcription factor jun-D

K04464

MAPK7; mitogen-activated protein kinase 7 [EC:2.7.11.24]

K04467

IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10]

K04502

FOSL1; fos-like antigen 1

K04519

IL1B; interleukin 1 beta

K04687

IFNG; interferon gamma

K04734

NFKBIA; NF-kappa-B inhibitor alpha

K04735

RELA; transcription factor p65

K05164

IL17RA, CD217; interleukin 17 receptor A

K05165

IL17RB, IL17RH1; interleukin 17 receptor B

K05166

IL17RC, IL17RL; interleukin 17 receptor C

K05168

IL17RE; interleukin 17 receptor E

K05405

IL6; interleukin 6

K05410

TBK1; TANK-binding kinase 1 [EC:2.7.11.10]

K05423

CSF3, GCSF; granulocyte colony-stimulating factor

K05427

CSF2, GMCSF; granulocyte-macrophage colony-stimulating factor

K05428

IL5; interleukin 5

K05430

IL4; interleukin 4

K05435

IL13; interleukin 13

K05489

IL17A, CTLA8; interleukin 17A

K05490

IL17B, CX1; interleukin 17B

K05491

IL17C, CX2; interleukin 17C

K05492

IL17D, IL27; interleukin 17D

K05493

IL17E, IL25; interleukin 17E

K05494

IL17F, ML1; interleukin 17F

K05505

CXCL1_2_3, GRO; C-X-C motif chemokine 1/2/3

K05506

CXCL5_6, SCYB5_6; C-X-C motif chemokine 5/6

K05509

CCL7; C-C motif chemokine 7

K06855

MAPK4_6; mitogen-activated protein kinase 4/6 [EC:2.7.11.24]

K07209

IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]

K07210

IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma

K07211

IKBKE, IKKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10]

K07994

MMP13; matrix metalloproteinase-13 (collagenase 3) [EC:3.4.24.-]

K09029

FOSB; protein FosB

K09487

HSP90B, TRA1; heat shock protein 90kDa beta

K09848

TRAF4; TNF receptor-associated factor 4

K09849

TRAF5; TNF receptor-associated factor 5

K10030

IL8, CXCL8; interleukin 8

K10048

CEBPB; CCAAT/enhancer binding protein (C/EBP), beta

K11849

USP25; ubiquitin carboxyl-terminal hydrolase 25 [EC:3.4.19.12]

K11859

TNFAIP3, A20, OTUD7C; tumor necrosis factor, alpha-induced protein 3 [EC:3.4.19.12]

K11987

PTGS2, COX2; prostaglandin-endoperoxide synthase 2 [EC:1.14.99.1]

K12671

CXCL10, IP10; C-X-C motif chemokine 10

K12793

MAP3K7IP3, TAB3; TAK1-binding protein 3

K12890

SRSF1, SFRS1, ASF, SF2; serine/arginine-rich splicing factor 1

K13088

ELAVL1, HUR; ELAV-like protein 1

K13908

MUC5; mucin-5

K14624

CCL2, MCP1; C-C motif chemokine 2

K14625

CCL20; C-C motif chemokine 20

K16597

CCL11; C-C motif chemokine 11

K19603

MAPK15; mitogen-activated protein kinase 15 [EC:2.7.11.24]

K21083

CCL17; C-C motif chemokine 17

K21100

DEFB4; beta-defensin 4

K21124

TRAF3IP2, ACT1; adaptor protein CIKS

K21126

S100A7; protein S100-A7

K21127

S100A8; protein S100-A8

K21128

S100A9; protein S100-A9

K21129

LCN2; lipocalin 2

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