Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression

Maitra, Amarnath; Shen, Fang; Hanel, Walter; Mossman, Karen; Tocker, Joel; Swart, David; Gaffen, Sarah L.

doi:10.1073/pnas.0611589104

Cited by 143 publications

(196 citation statements)

References 65 publications

Supporting

Mentioning

188

Contrasting

Order By: Relevance

“…It is not clear whether C/EBPβ and C/EPBδ are functionally redundant in terms of IL-17 signaling, as C/EBPβ and C/EBPδ can individually rescue C/EBPβδ-deficient cells for IL-6 promoter activity [72]. However, our recent analysis of the IL-17 receptor demonstrated that a mutant IL-17RA that can activate C/EBPδ but not C/EBPβ is compromised in the induction of some but not all IL-17 target genes [135], suggesting preference for C/EBPβ in some target genes.…”

Section: Ccaat/enhancer Binding Proteins (C/ebp)-in a Microarray Scrementioning

confidence: 92%

Structure–function relationships in the IL-17 receptor: Implications for signal transduction and therapy

Shen¹,

Gaffen²

2008

Cytokine

Self Cite

239

245

View full text Add to dashboard Cite

IL-17 is the defining cytokine of a newly-described "Th17" population that plays critical roles in mediating inflammation and autoimmunity. The IL-17/IL-17 receptor superfamily is the most recent class of cytokines and receptors to be described, and until recently very little was known about its function or molecular biology. However, in the last year important new insights into the composition and dynamics of the receptor complex and mechanisms of downstream signal transduction have been made, which will be reviewed here.

show abstract

Section: Ccaat/enhancer Binding Proteins (C/ebp)-in a Microarray Scrementioning

confidence: 92%

Structure–function relationships in the IL-17 receptor: Implications for signal transduction and therapy

Shen¹,

Gaffen²

2008

Cytokine

Self Cite

239

245

View full text Add to dashboard Cite

show abstract

“…However, a region called TIR-like loop is only found at the C-terminal of SEFIR of IL-17RA. 24 This may explain why IL-17RA functions as a common subunit to all other IL-17Rs in the family. Subsequently, ACT1 (also known as CIKS), an activator of NF-kB that previously linked to B cellactivating factor and CD40L signaling, was found to contain a SEFIR domain.…”

Section: Signal Transduction Of Il-17mentioning

confidence: 99%

“…Deletion or point mutation of this domain in IL-17RA impairs the activation of NF-kB by IL-17A. 24 Further analysis revealed that SEFIR lacks the BB-loop, 23 the crucial specificity component of TIR domains, perhaps explaining why it cannot engage TLR-associated adaptors 24,25 and suggesting the existence of different intermediates. However, a region called TIR-like loop is only found at the C-terminal of SEFIR of IL-17RA.…”

Section: Signal Transduction Of Il-17mentioning

confidence: 99%

“…28 ACT1 is required for the transcription of C/EBP-d but is not essential for C/EBP-b. 24 Additional mechanisms independent of ACT1 have also been recently implicated in IL-17A signaling in human airway epithelial cells. In this pathway, IL-17A activates Janus kinasemediated phosphatidylinositol 3-kinase and subsequently inactivates glycogen synthase kinase-3b.…”

Section: Il-17 and Its Biological Functions S Xu And Xt Cao 165mentioning

confidence: 99%

“…16 The IL-17 receptors also constitute a distinct family of cytokine receptors; the family includes IL-17RA, IL-17RB, IL-17RC, IL-17RD and IL-17RE, 17 all of which are type I transmembrane proteins. IL-17RA (or IL-17R) was the first described IL-17 receptor, 2,19 and it binds IL-17A with higher affinity than IL-17F in human. IL-17RA appears to be ubiquitously expressed in hematopoietic tissues, 2,18 various myeloid cells, epithelial cells, fibroblasts, endothelial cells, epithelial cells and osteoblasts.…”

Section: Il-17 and Its Receptorsmentioning

confidence: 99%

See 2 more Smart Citations

Interleukin-17 and its expanding biological functions

2010

View full text Add to dashboard Cite

Interleukin-17 (IL-17) and IL-17-producing cells have been shown to play important roles in inflammation and the immune response. IL-17 is believed to be mainly produced by T helper 17 (Th17) cells, a unique helper T-cell subset different from Th1 and Th2 cells. Other subsets of T cells such as cdT and natural killer T (NKT) cells have also been found to produce IL-17 in response to innate stimuli. IL-17 acts as a proinflammatory cytokine that can induce the release of certain chemokines, cytokines, matrix metalloproteinases (MMPs) and antimicrobial peptides from mesenchymal and myeloid cells. This leads to the expansion and accumulation of neutrophils in the innate immune system and links innate and adaptive immunity in vivo. Furthermore, increasing evidence indicates that IL-17 and IL-17-producing cells are involved in the pathogenesis of various diseases such as allergies, autoimmune diseases, allograft transplantation and even malignancy. They may also play protective roles in host defense against infectious diseases and promote induction of cytotoxic T lymphocyte (CTL) responses against cancer. Targeting of the IL-17 axis is under investigation for the treatment of inflammatory disorders.

show abstract

Regulation of the Stem Cell–Host Immune System Interplay Using Hydrogel Coencapsulation System with an Anti‐Inflammatory Drug

Moshaverinia

Chen

et al. 2015

Adv Funct Materials

View full text Add to dashboard Cite

The host immune system is known to influence mesenchymal stem cell (MSC)-mediated bone tissue regeneration. However, the therapeutic capacity of hydrogel biomaterial to modulate the interplay between MSCs and T-lymphocytes is unknown. Here it is shown that encapsulating hydrogel affects this interplay when used to encapsulate MSCs for implantation by hindering the penetration of pro-inflammatory cells and/or cytokines, leading to improved viability of the encapsulated MSCs. This combats the effects of the host pro-inflammatory T-lymphocyte-induced nuclear factor kappaB pathway, which can reduce MSC viability through the CASPASE-3 and CAS-PASE-8 associated proapoptotic cascade, resulting in the apoptosis of MSCs. To corroborate rescue of engrafted MSCs from the insult of the host immune system, the incorporation of the anti-inflammatory drug indomethacin into the encapsulating alginate hydrogel further regulates the local microenvironment and prevents pro-inflammatory cytokine-induced apoptosis. These findings suggest that the encapsulating hydrogel can regulate the MSC-host immune cell interplay and direct the fate of the implanted MSCs, leading to enhanced tissue regeneration.

show abstract

Distinct functional motifs within the IL-17 receptor regulate signal transduction and target gene expression

Cited by 143 publications

References 65 publications

Structure–function relationships in the IL-17 receptor: Implications for signal transduction and therapy

Structure–function relationships in the IL-17 receptor: Implications for signal transduction and therapy

Interleukin-17 and its expanding biological functions

Regulation of the Stem Cell–Host Immune System Interplay Using Hydrogel Coencapsulation System with an Anti‐Inflammatory Drug

Contact Info

Product

Resources

About