IL-17A In CD4 Research Articles

Altered Balance Between IL-17A– and IL-17F–Producing Th17 Cells in HIV-Infected Patients

Altered Balance Between IL-17A– and IL-17F–Producing Th17 Cells in HIV-Infected Patients

Sa1701 Smad7-Mediated Suppression of IL-17A in CD4+ T Cells Prevents Early but Not Late Stage Colorectal Cancer Development

Sa1701 Smad7-Mediated Suppression of IL-17A in CD4+ T Cells Prevents Early but Not Late Stage Colorectal Cancer Development

Disturbed Th1, Th2, Th17 and Treg balance in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by disturbed T-cell homeostasis. Dysbalance of T-helper-cell (Th) subsets (Th1/Th2/Th17) and regulatory T-cells (T(regs)) is suggested to contribute to the pathogenesis of SLE. Recent reports suggest functional deviation of T(regs) in terms of producing IL-17A, a process that may be aberrant in SLE. Therefore, we analyzed these T-cell subsets in SLE to test the hypothesis that aberrant T-cell subset skewing is present in SLE-patients. We investigated simultaneously the intracellular cytokines IFN-γ, IL-4 and IL-17A in CD4(+)T-cells as well as in T(regs). Skewing of T-cell subsets towards Th17 cells was observed in SLE-patients. Although the proportion of T(regs) was similar between SLE-patients and healthy controls, the ability of T(regs) to express IFN-γ and IL17A was impaired in SLE-patients. Even in quiescent SLE-patients T-cell homeostasis is aberrant in terms of skewing towards IL-17 producing T-cells.

Abstract 5324: Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis

Abstract The intestinal tract is subject to constant stimulation of immune cells and intestinal epithelial cells either by noninfectious antigens or infection. Recent studies identified the role of IL-17A in chronic inflammation in intestinal epithelium. Yet the intrinsic role of endogenous IL-17A in spontaneous intestinal tumorigenesis has not been addressed previously. Ablation of IL-17A significantly reduced tumor development in mice bearing a heterozygote mutation in the APC (adenomatous polyposis coli) gene (ApcMin/+ mice). There was a marked decrease in IL-6 and IL-23 (p19), as well as a decrease in IL-1β, suggesting that the inflammatory microenvironment was significantly changed by ablating IL-17A. We also found a significant decrease in CD44 and proinflammatory mediators such as KC (Keratinocyte Chemoattractant) and Cox-2. There was also a reduced infiltration of lymphocytes including T cells and preservation of intestinal architecture and the presence of APC protein in intestinal epithelial cells in IL-17AKO ApcMin/+ mice. Interestingly, IL-17A ablation also corrected immunological abnormalities such as splenomegaly and thymic atrophy in ApcMin/+ mice. We tested whether CD4 T cells from ApcMin/+ mice are more proliferative based on its role as a tumor suppressor gene, thereby regulating cell cycle. We observed that CD4 T cells from ApcMin/+ mice were hyperproliferative when compared with their wildtype littermate controls upon TcR (T cell receptor) stimulation. This hyperproliferation was more obvious following stronger stimulation through the TcR. Next, we tested whether the effector CD4 T cells are more refractory to regulatory T cell (Treg)-mediated suppression. Upon co-culture with wildtype Treg cells, ApcMin/+ CD4 effector T cells were more resistant to Treg-mediated suppression especially at a high ratio of effectors to Treg, suggesting that the suppression on ApcMin/+ CD4 effector T cells are not as efficient as for wildtype CD4 effector T cells. Finally, these CD4 T cells from ApcMin/+ mice induced colitis in immunodeficient mice upon adoptive transfer, while the ablation of IL-17A in CD4 T cells in ApcMin/+ mice (IL-17A KO ApcMin/+ mice) completely abolished this pathogenic potential in vivo, clearly showing that ablation of IL-17A abrogated hyperproliferation and colitogenic potential in immunodeficient mice. This was consistent with our observation of the phenotypic changes in intestinal tumorigenesis. Taken together, our results suggest an important proinflammatory role of IL-17A and its correction of immune abnormalities in spontaneous intestinal tumorigenesis. We demonstrate altered CD4 T cell functions from ApcMin/+ mice which favors intestinal tumorigenesis and the ablation of IL-17A can abolish these altered function, suggesting the importance of T-cell mediated IL-17A in spontaneous intestinal tumorigenesis Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5324.

Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis

The intrinsic role of endogenous IL-17A in spontaneous intestinal tumorigenesis has not been addressed previously to our knowledge. Ablation of IL-17A significantly reduced tumor development in mice bearing a heterozygote mutation in the adenomatous polyposis coli (APC) gene (Apc(Min/+) mice). There was also a decrease in inflammatory cytokines and proinflammatory mediators, reduced infiltration of lymphocytes including T cells, and preservation of intestinal architecture and the presence of APC protein in intestinal epithelial cells. Interestingly, IL-17A ablation also corrected immunological abnormalities such as splenomegaly and thymic atrophy in Apc(Min/+) mice. CD4 T cells from Apc(Min/+) mice showed hyperproliferative potential in vitro and in vivo and increased levels of IL-17A and IL-10. The effector CD4 T cells from Apc(Min/+) mice were more resistant to regulatory T cell-mediated suppression. Finally, these CD4 T cells induced colitis in immunodeficient mice upon adoptive transfer, whereas the ablation of IL-17A in CD4 T cells in Apc(Min/+) mice completely abolished this pathogenic potential in vivo. Taken together, our results show that CD4 T cell-derived IL-17A promotes spontaneous intestinal tumorigenesis with altered functions of CD4 T cells in Apc(Min/+) mice.