Dataset Information

Effects of Anti-TNF? Treatment on Mucosal Expression of IL-17A, IL-21, and IL-22 and Cytokine-Producing T Cell Subsets in Crohn's Disease.

ABSTRACT: T helper 17 (Th17) cells produce interleukin (IL) 17-A. In addition, Th17 cells produce IL-21 and IL-22. Th17 cells have a disease-promoting role in Crohn's disease (CD). We investigated the effects of anti-TNF? treatment on mucosal gene expression (qPCR) of IL-17A, IL-21, and IL-22 as well as on the frequency of lamina propria (LP) T cell subsets producing these cytokines (flow cytometry) in 12 active CD patients before and after 4 weeks of anti-TNF? treatment with adalimumab. At baseline, in inflamed mucosa we found increased gene expression of IL-17A and IL-22 but not IL-21 when compared to noninflamed mucosa. There were increased frequencies of IL-21-producing LP T cells but no differences in the frequencies of IL-17A- or IL-22-producing LP T cells when comparing inflamed versus noninflamed mucosa at baseline. There were no changes in the mucosal gene expression of IL-17A, IL-21, and IL-22 or the frequencies of IL-17A-, IL-21- and IL-22-producing LP T cell subsets between baseline and following 4 weeks of adalimumab initiation. Our results do not support the hypothesis that anti-TNF? treatment has an early effect on the mucosal levels of IL-17A, IL-21, and IL-22 or LP T cell production of these cytokines in CD.

SUBMITTER: Dige A

PROVIDER: S-EPMC5944277 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of Anti-TNFα Treatment on Mucosal Expression of IL-17A, IL-21, and IL-22 and Cytokine-Producing T Cell Subsets in Crohn's Disease.

Dige Anders A Magnusson Maria K MK Uhrenholt Claus C Rasmussen Tue Kruse TK Kragstrup Tue T Öhman Lena L Dahlerup Jens J Agnholt Jørgen J

Mediators of inflammation 20180426

T helper 17 (Th17) cells produce interleukin (IL) 17-A. In addition, Th17 cells produce IL-21 and IL-22. Th17 cells have a disease-promoting role in Crohn's disease (CD). We investigated the effects of anti-TNFα treatment on mucosal gene expression (qPCR) of IL-17A, IL-21, and IL-22 as well as on the frequency of lamina propria (LP) T cell subsets producing these cytokines (flow cytometry) in 12 active CD patients before and after 4 weeks of anti-TNFα treatment with adalimumab. At ...[more]

PMID: 29853788

Similar Datasets

Project description:RationaleNeutrophils constitute massive cellular constituents in inflammatory human gastric cancer (GC) tissues, but their roles in pathogenesis of inflammatory T helper (Th) subsets are still unknown.MethodsFlow cytometry analysis and immunohistochemistry were used to analyze the responses and phenotypes of neutrophils in different samples from 51 patients with GC. Kaplan-Meier plots and Multivariate analysis for the survival of patients were used by log-rank tests and Cox proportional hazards models. Neutrophils and CD4+ T cells were purified and cultured for ex vivo, in vitro and in vivo regulation and function assays.ResultsGC patients exhibited increased tumoral neutrophil infiltration with GC progression and poor patient prognosis. Intratumoral neutrophils accumulated in GC tumors via CXCL6/CXCL8-CXCR1-mediated chemotaxis, and expressed activated molecule CD54 and co-signaling molecule B7-H2. Neutrophils induced by tumors strongly expressed CD54 and B7-H2 in both dose- and time-dependent manners, and a close correlation was obtained between the expressions of CD54 and B7-H2 on intratumoral neutrophils. Tumor-derived tumor necrosis factor-α (TNF-α) promoted neutrophil activation and neutrophil B7-H2 expression through ERK-NF-κB pathway, and a significant correlation was found between the levels of TNF-α and CD54+ or B7-H2+ neutrophils in tumor tissues. Tumor-infiltrating and tumor-conditioned neutrophils effectively induced IL-17A-producing Th subset polarization through a B7-H2-dependent manner ex vivo and these polarized IL-17A-producing Th cells exerted protumorigenic roles by promoting GC tumor cell proliferation via inflammatory molecule IL-17A in vitro, which promoted the progression of human GC in vivo; these effects could be reversed when IL-17A is blocked. Moreover, increased B7-H2+ neutrophils and IL-17A in tumors were closely related to advanced GC progression and predicted poor patient survival.ConclusionWe illuminate novel underlying mechanisms that TNF-α-activated neutrophils link B7-H2 to protumorigenic IL-17A-producing Th subset polarization in human GC. Blocking this pathological TNF-α-B7-H2-IL-17A pathway may be useful therapeutic strategies for treating GC.

Dataset Information

Effects of Anti-TNF? Treatment on Mucosal Expression of IL-17A, IL-21, and IL-22 and Cytokine-Producing T Cell Subsets in Crohn's Disease.

Publications

Effects of Anti-TNF<i>α</i> Treatment on Mucosal Expression of IL-17A, IL-21, and IL-22 and Cytokine-Producing T Cell Subsets in Crohn's Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets