Disease relevance of Il17a

• This establishes IL-17A as a hemopoietic response cytokine to radiation injury in mice and an inducible mechanism that is required for recovery of granulopoiesis after radiation injury [1].
• Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor [2].
• We found that contact, delayed-type, and airway hypersensitivity responses, as well as T-dependent antibody production, were significantly reduced in the mutant mice, while IL-17 deficiency of donor T cells did not affect acute graft-versus-host reaction [3].
• Here we demonstrate that IL-27Ralpha-deficient mice were hypersusceptible to experimental autoimmune encephalomyelitis and generated more IL-17-producing T helper cells [4].
• It was recently demonstrated that interleukin (IL)-23-driven IL-17-producing (ThIL-17) T cells mediate inflammatory pathology in certain autoimmune diseases [5].
• Impaired granuloma formation was also observed in the infected lungs of IL-17-deficient mice, which is consistent with the decreased delayed-type hypersensitivity response of the infected mice against mycobacterial Ag [6].

Psychiatry related information on Il17a

• The effects of alcohol consumption on pulmonary release of IL-17 are unknown [7].
• CONCLUSIONS: The results of these experiments strongly implicate IL-17 as an important pathway for the immunosuppression associated with alcohol abuse and support gene therapeutic approaches to augment immune function in the alcoholic host or to treat infections associated with alcoholism [7].

High impact information on Il17a

• Intestinal inflammation was associated with IL-23 (p19) mRNA-producing intestinal dendritic cells and IL-17A mRNA within the intestine [8].
• TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells [9].
• Treg can be substituted by TGFbeta1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1beta and TNFalpha [9].
• Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells [9].
• The range of identified effector CD4 T cell lineages has recently expanded with description of an IL-17-producing subset, called Th17, which develops via cytokine signals distinct from, and antagonized by, products of the Th1 and Th2 lineages [10].

Chemical compound and disease context of Il17a

• Resident V{delta}1+ {gamma}{delta} T Cells Control Early Infiltration of Neutrophils after Escherichia coli Infection via IL-17 Production [11].

Biological context of Il17a

• STAT3 and NF-{kappa}B Signal Pathway Is Required for IL-23-Mediated IL-17 Production in Spontaneous Arthritis Animal Model IL-1 Receptor Antagonist-Deficient Mice [12].
• Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17 [13].
• Collectively, these data show that severe IL-17-mediated EAM can develop in the absence of T-bet, and that T-bet can regulate autoimmunity via the control of nonspecific CD8+ T cell bystander functions in the inflamed target organ [14].
• We also show that IL-23 is required for the induction of an IL-17-producing Ag-specific phenotype in naive CD4 T cells in vitro and that absence of IL-12p70 promotes an increase in the number of IL-17-producing Ag-specific CD4 T cells both in vitro and in vivo [15].
• Neutralization of IL-17 significantly prevented joint swelling at day 1 of flare and significantly suppressed joint inflammation and cartilage proteoglycan depletion at day 4, as assessed by histology [16].

Anatomical context of Il17a

• IL-23 has proinflammatory activity, inducing IL-17 secretion from activated CD4(+) T cells and stimulating the proliferation of memory CD4(+) T cells [12].
• We found that the culture supernatant of mouse resident peritoneal exudate cells (PEC) cocultured with FasL-expressing tumor (FFL) cells induced IL-17 production in freshly isolated resident PEC [17].
• In these analyses, as little as 20 pg of peritoneal IL-17 induced neutrophil infiltration [18].
• This curbs phagocyte secretion of IL-23, a cytokine controlling IL-17 production by Tn cells [13].
• In embryonic fibroblasts (EFs) derived from TRAF6 knockout mice, IL-17 failed to activate the IkappaB kinases (IKKs) and JNK [19].

Associations of Il17a with chemical compounds

• Local IL-17 promoted osteoclastic bone destruction, which was accompanied with marked tartrate-resistant acid phosphatase activity at sites of bone erosion in cortical, subchondral, and trabecular bone [20].
• Our findings indicate that IL-17 plays an important role in activating T cells in allergen-specific T cell-mediated immune responses [3].
• Induction of G-CSF expression in 3T3 cells by IL-17 did not appear to require tyrosine kinase activation or de novo protein synthesis [21].
• Antibody-independent, interleukin-17A-mediated, cross-serotype immunity to pneumococci in mice immunized intranasally with the cell wall polysaccharide [22].
• A similar pattern was observed for IL-17, supporting a contribution of T cells to the neutrophilic inflammation only at high-dose exposure to LPS [23].
• The synergy between TNF-alpha and IL-17 reflects their independent actions on KC gene expression; TNF-alpha serves as a stimulus to initiate transcription through activation of NF-kappaB, whereas IL-17 drives mRNA stabilization through an Act1-dependent pathway [24].
• Airway neutrophilia was abolished by a single treatment with neutralizing monoclonal antibody against IL-17 before alpha-GalCer administration [25].

Physical interactions of Il17a

• Stability studies revealed that IL-17 stabilized G-CSF mRNA levels, with a t1/2 of 4 h, compared to a t1/2 of less than 2 h in medium or LPS-treated cells [21].

Regulatory relationships of Il17a

• Tumor necrosis factor alpha also synergized with IL-23 to enhance IL-17 production, and this was IL-1 dependent [5].
• IL-23 alone did not induce IL-17 production by T cells from IL-1RI(-/-) mice, and IL-23-induced IL-17 production was substantially enhanced by IL-1alpha or IL-1beta, even in the absence of T cell receptor stimulation [5].
• In conclusion, IL-17 stimulated NO production by an NF-kappaB-dependent pathway in osteoblastic cells and fetal mouse metatarsals only in combination with TNF-alpha [26].
• In vitro, IL-15 was able to induce IL-17 release from purified spleen CD4(+) cells, but not spleen CD8(+) or airway neutrophils [27].
• The combination of IL-17 and LPS enhanced G-CSF expression in an additive fashion [21].
• Ligation of either TCR or IL-23R triggered IL-17 production and both together had a synergistic effect, suggesting independent but convergent pathways [28].

Other interactions of Il17a

• Interestingly, bacillus Calmette-Gu??rin immune T cells generated in the absence of IL-12 or IL-23 were deficient in IFN-gamma production, but exhibited a robust IL-17 secretion associated with a degree of protection against pulmonary infection [29].
• IL-1beta further increased the production of IL-23, which induced IL-17 production and OX40 expression in splenic CD4(+) T cells of IL-1Ra(-/-) mice [12].
• Involvement of IL-17 in Fas ligand-induced inflammation [18].
• Antibodies neutralising interleukin (IL)-1alpha, IL-1beta, soluble IL-6 receptor, IL-17, or tumour necrosis factor-alpha, when added to individual SFs, only occasionally decreased the bone-resorbing activity [30].
• Messenger RNA levels of IL-17, IL-12, and cathepsin K in the synovial tissue were suppressed, as were IL-6 and IL-12 protein production [31].
• The results apply to initial generation of the IL-17 phenotype because naive CD62L(high) Daf1(-/-) T cells produce 3-fold more IL-17 in response to TGF-beta and IL-6, whereas CD62L(high) Daf1(-/-)C5aR(-/-)C3aR(-/-) T cells produce 4-fold less [32].

Analytical, diagnostic and therapeutic context of Il17a

• IL-4 gene therapy for collagen arthritis suppresses synovial IL-17 and osteoprotegerin ligand and prevents bone erosion [31].
• Adoptive transfer of wild-type, but not adhesion molecule-deficient, neutrophils into mice deficient in beta2 integrins transiently decreases neutrophilia and reduces levels of serum IL-17 [13].
• Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice [33].
• In the bronchoalveolar lavage cells, IL-17 mRNA was detected at days 1, 2, and 3 postchallenge, with a strong expression at day 2 [27].
• Confocal laser-scanning microscopy analysis revealed that CD4(+) T cells comprise the abscess wall in these animals and produce IL-17 at this site [34].

References