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- W4313360043 abstract "Abstract Hypersensitivity pneumonitis (HP) is a lung disease caused by repeated inhalation of environmental antigens leading to inflammation, tissue scarring, and impaired lung function. This pathology is associated with IL-17A-producing Th17 cells and recruitment of inflammatory cells such as neutrophils to the lungs; on the other hand, Foxp3+ regulatory T (Treg) cells play a protective rolein HP by suppressing pathogenic T cell functions. The thermophile Saccharopolyspora rectivirgula (SR) causes HP in humans, attributed to the rare farmers’ lung disease. We used a murine model carrying the IL-17AGFP/Foxp3RFP dual reporters in SR-induced HP, to study the cellular and molecular mechanisms of HP disease development. IL-2-inducible T cell Kinase, ITK is downstream of the T cell receptor, and is required for effective differentiation of Th17 cells, but limits the expansion of Treg cells. In this work, we sought to determine the possibility of using ITK as a target for pharmaceutical inhibitors in HP. To evaluate the effect of targeting ITK kinase activity in HP therapy, we utilized an Itk allele sensitive mutant (Itkas) that allows specific inhibition by a compound 3MBPP1. WT, Itk−/− and ItkasIL-17AGFP/Foxp3RFP mice exposed to SR were treated with 3MBPP and analyzed for histopathology and various immune cell populations. Intranasal delivery of 3MBPP1 for up to 4 weeks affected pathogenesis and targeted primarily the bronchoalveolarlavage (BAL) immune subsets, including CD4+ IL-17A+ cells. In addition, Treg cells in the pulmonary lymph nodes, neutrophils in the lungs, and γδ T cells in all organs were affected by the treatment. These data suggest that ITK may be a therapeutic target for HP that involves the IL-17 and Foxp3-expressing T cell subsets." @default.
- W4313360043 created "2023-01-06" @default.
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- W4313360043 date "2017-05-01" @default.
- W4313360043 modified "2023-09-23" @default.
- W4313360043 title "<i>Itk:</i> A potential target for <i>Saccharopolyspora rectivirgula-</i>induced hypersensitivity pneumonitis" @default.
- W4313360043 doi "https://doi.org/10.4049/jimmunol.198.supp.123.14" @default.
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