IL-17RD (Sef or IL-17RLM) interacts with IL-17 receptor and mediates IL-17 signaling

Rong, Zhili; Wang, Anan; Li, Zhiyong; Ren, Yongming; Cheng, Long; Li, Yinghua; Wang, Yinyin; Ren, Fei; Zhang, Xiaoning; Hu, Jim; Chen, Zhijie

doi:10.1038/cr.2008.320

Cited by 76 publications

(60 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, NF-κB recruitment to the 24p3 promoter has been reported to be dependent on p38 MAPK activity 30 and thus the presently described role for IL-17RD in mediating IL-17-induced activation of p38 MAPK may underlie the ability of IL-17RD to activate the 24p3 promoter 23 . Collectively, these data indicate that IL-17RD is an important functional regulator of IL-17A-induced signalling.…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia

et al. 2012

View full text Add to dashboard Cite

Interleukin-17A, the prototypical member of the interleukin-17 cytokine family, coordinates local tissue inflammation by recruiting neutrophils to sites of infection. Dysregulation of interleukin-17 signalling has been linked to the pathogenesis of inflammatory diseases and autoimmunity. The interleukin-17 receptor family members (A-E) have a broad range of functional effects in immune signalling yet no known role has been described for the remaining orphan receptor, interleukin-17 receptor D, in regulating interleukin-17A-induced signalling pathways. Here we demonstrate that interleukin-17 receptor D can differentially regulate the various pathways employed by interleukin-17A. neutrophil recruitment, in response to in vivo administration of interleukin-17A, is abolished in interleukin-17 receptor D-deficient mice, correlating with reduced interleukin-17A-induced activation of p38 mitogen-activated protein kinase and expression of the neutrophil chemokine mIP-2. In contrast, interleukin-17 receptor D deficiency results in enhanced interleukin-17A-induced activation of nuclear factor-kappa B and interleukin-6 and keratinocyte chemoattractant expression. Interleukin-17 receptor D disrupts the interaction of Act1 and TRAF6 causing differential regulation of nuclear factorkappa B and p38 mitogen-activated protein kinase signalling pathways.

show abstract

Section: Discussionmentioning

confidence: 98%

“…Previously, it has been reported that IL-17RD promotes IL-17A-induced signalling based on its ability to activate a 24p3 native promoter 23 . 24p3 or murine lipocalin-2 (also known as SIP24) is an IL-17-inducible gene that is dependent on NF-κB activation 29 .…”

Section: Discussionmentioning

confidence: 99%

Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia

et al. 2012

View full text Add to dashboard Cite

show abstract

“…30 IL-17RD was recently suggested to be a positive component in IL-17 signaling and a negative suppressor for TLRs signaling. [31][32][33] However, the detailed molecular mechanisms underlying the roles of IL-17RD in these pathways are unknown, and whether there is a functional ligand for IL-17RD remains an open question in this field.…”

Section: Overview Of Il-17 Family Cytokinesmentioning

confidence: 99%

The roles and functional mechanisms of interleukin-17 family cytokines in mucosal immunity

et al. 2016

View full text Add to dashboard Cite

The mucosal immune system serves as our front-line defense against pathogens. It also tightly maintains immune tolerance to self-symbiotic bacteria, which are usually called commensals. Sensing both types of microorganisms is modulated by signalling primarily through various pattern-recognition receptors (PRRs) on barrier epithelial cells or immune cells. After sensing, proinflammatory molecules such as cytokines are released by these cells to mediate either defensive or tolerant responses. The interleukin-17 (IL-17) family members belong to a newly characterized cytokine subset that is critical for the maintenance of mucosal homeostasis. In this review, we will summarize recent progress on the diverse functions and signals of this family of cytokines at different mucosal edges.

show abstract

“…It is not clear whether the same extended sequences of IL-17RA are required for responses to IL-25. IL-17RA has also been suggested to partner with IL-17RD (SEF) (38), although the ligand that binds to this pairing is unknown.…”

Section: Discussionmentioning

confidence: 99%

SEF/IL-17R (SEFIR) Is Not Enough

Onishi

Park

Hanel

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

IL-17, the hallmark cytokine of the Th17 population, mediates immunity to extracellular pathogens and promotes autoimmune immunopathology. The signaling mechanisms triggered by the IL-17 receptor (IL-17RA) and related receptors are strikingly different from other cytokine subclasses. Namely, IL-17Rs contain a conserved SEF/IL-17R (SEFIR) subdomain that engages Act1, leading to activation of TRAF6, NF-B, and other events. Although the SEFIR is critical for signaling, the molecular details of the functional subdomains within IL-17RA remain poorly characterized. Here, we provide a detailed structurefunction analysis delineating the C-terminal boundary of the SEFIR-containing region of IL-17RA. We show that functionality of this domain requires a large extension to the previously identified SEFIR motif. In contrast to the SEFIR, this extension is not conserved among IL-17R family members. Surprisingly, Act1 recruitment is not sufficient for downstream signaling activation, whereas ubiquitination of TRAF6 correlates tightly with functional receptors. We further demonstrate that IL-17RA exhibits signaling properties that are nonredundant with other IL-17R family members. Finally, we report that IL-17 signals synergistically with lymphotoxin-␣3, using the same signaling motifs within IL-17RA. These studies provide new insight into the structure-function relationships of IL-17RA and reveal distinct signaling differences among IL-17R family members.

show abstract

IL-17RD (Sef or IL-17RLM) interacts with IL-17 receptor and mediates IL-17 signaling

Cited by 76 publications

References 46 publications

Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia

Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia

The roles and functional mechanisms of interleukin-17 family cytokines in mucosal immunity

SEF/IL-17R (SEFIR) Is Not Enough

Contact Info

Product

Resources

About