OR.74. Cd8+ Il-17 Producing T-Cells Are Important in Effector Functions for the Elicitation of Contact Hypersensitivity

He, Dao-Yao; Wu, Lizhi; Kim, Hee Kyung; Li, Hui; Elmets, Craig A.; Xu, Hui

doi:10.1016/j.clim.2006.04.230

Cited by 2 publications

(3 citation statements)

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“…It has anti-inflammatory roles inhibiting Th1 and Th2 differentiation and maturation of macrophages and dendritic cells, and it also induces T regulatory cells (19)(20)(21)(22). On the other hand, TGF-ß has a proinflammatory effect by enhancing leukocyte recruitment, IgA production, chemoattracting leucocytes and by modulating adhesion molecules (23,24). A study onSMAD3 knockout mice revealed increases in Th2 and IL17 proinflammatory pathways and also induced regulatory elements like Foxp3 (25).…”

Section: Discussionmentioning

confidence: 99%

Association of asthma genetic variants with asthma-associated traits reveals molecular pathways of eosinophilic asthma

El‐Husseini

Vonk

Berge

et al. 2022

Preprint

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Introduction: Asthma is a complex, polygenic, heterogenous inflammatory disease. Recently, we generated a list of 128 independent single nucleotide polymorphisms (SNPs) associated with asthma in genome-wide association studies. However, it is unknown if asthma SNPs are associated with specific asthma-associated traits such as high eosinophil counts, atopy, and airway obstruction, revealing molecular endotypes of this disease. Here, we aim to identify the association between asthma SNPs and asthma-associated traits and assess e-QTLs to reveal their downstream functional effects and find drug targets. Methods: Association analyses between 128 asthma SNPs and associated traits (blood eosinophil numbers, atopy, airway obstruction, airway hyperresponsiveness) were conducted using regression modelling in population-based studies (Lifelines N=32,817 / Vlagtwedde-Vlaardingen N=1,554) and an asthma cohort (Dutch Asthma GWAS N=917). Functional enrichment and pathway analysis were performed with genes linked to the significant SNPs by e-QTL analysis. Genes were investigated to generate novel drug targets. Results: We identified 69 asthma SNPs that were associated with at least one trait, with 20 SNPs being associated with multiple traits. The SNP annotated to SMAD3 was the most pleiotropic. In total, 42 SNPs were associated with eosinophil counts, 18 SNPs with airway obstruction, and 21 SNPs with atopy. We identified genetically driven pathways regulating eosinophilia, atopy and airway obstruction. The largest network of eosinophilia contained two genes ( IL4R, TSLP) targeted by drugs currently available for eosinophilic asthma. Several novel targets were identified. Conclusion: Many asthma SNPs are associated with blood eosinophil counts and genetically driven molecular pathways of asthma-associated traits were identified.

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Section: Discussionmentioning

confidence: 99%

Association of asthma genetic variants with asthma-associated traits reveals molecular pathways of eosinophilic asthma

El‐Husseini

Vonk

Berge

et al. 2022

Preprint

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“…Increasing evidence from a number of studies suggests that effector cells that mediate CHS are interferon γ (IFN‐γ)–producing CD4 + T helper 1 (Th1) and CD8 + T cytotoxic 1 (Tc1) lymphocytes 5,6 . Moreover, IL‐17 is also required for hapten‐specific T‐cell sensitization, especially for CD4 + T cells, 7 whereas IL‐17‐producing CD8 + T‐cell effectors provoke CHS 8 …”

Section: Introductionmentioning

confidence: 99%

“…5,6 Moreover, IL-17 is also required for hapten-specific T-cell sensitization, especially for CD4 + T cells, 7 whereas IL-17-producing CD8 + T-cell effectors provoke CHS. 8 Inflammation plays an important role in obesity, with immune cell infiltration in the adipose tissue (AT) of obese humans and mice induced by a high-fat diet (HFD). 9 CD4 + Th1 cells, CD8 + Tc1 effector cells, and macrophages were found in the infiltrates of HFD-induced obese (HFDIO) mice, whereas the number of regulatory T cells was decreased.…”

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confidence: 99%

Obesity aggravates contact hypersensitivity reaction in mice

et al. 2022

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Background Obesity is associated with chronic, low‐grade inflammation in tissues and predisposes to various complications, including inflammatory skin diseases. However, the link between obesity and contact hypersensitivity (CHS) is not fully understood. Objectives We sought to determine the influence of obesity on T helper 1 (Th1)–mediated CHS. Methods The activity/phenotype/cytokine profile of the immune cells was tested in vivo and in vitro. Using quantitative polymerase chain reaction (qPCR) and fecal microbiota transplantation (FMT), we tested the role of a high‐fat diet (HFD)–induced gut microbiota (GM) dysbiosis in increasing the effects of CHS. Results Exacerbated CHS correlates with an increased inflammation‐inducing GM in obese mice. We showed a proinflammatory milieu in the subcutaneous adipose tissue of obese mice, accompanied by proinflammatory CD4+ T cells and dendritic cells in skin draining lymph nodes and spleen. Obese interleukin (IL)‐17A−/−B6 mice are protected from CHS aggravation, suggesting the importance of IL‐17A in CHS aggravation in obesity. Conclusions Obesity creates a milieu that induces more potent CHS‐effector cells but does not have effects on already activated CHS‐effector cells. IL‐17A is essential for the pathogenesis of enhanced CHS during obesity. Our study provides novel knowledge about antigen‐specific responses in obesity, which may help with the improvement of existing treatment and/or in designing novel treatment for obesity‐associated skin disorders.

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OR.74. Cd8+ Il-17 Producing T-Cells Are Important in Effector Functions for the Elicitation of Contact Hypersensitivity

Cited by 2 publications

References 0 publications

Association of asthma genetic variants with asthma-associated traits reveals molecular pathways of eosinophilic asthma

Association of asthma genetic variants with asthma-associated traits reveals molecular pathways of eosinophilic asthma

Obesity aggravates contact hypersensitivity reaction in mice

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