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    Reciprocal regulation of Th2 and Th17 cells by PAD2-mediated citrullination

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    Authors
    Sun, Bo
    Chang, Hui-Hsin
    Salinger, Ari J.
    Tomita, Beverly
    Bawadekar, Mandar
    Holmes, Caitlyn L.
    Shelef, Miriam A.
    Weerapana, Eranthie
    Thompson, Paul R
    Ho, I-Cheng
    UMass Chan Affiliations
    Thompson Lab
    Department of Biochemistry and Molecular Pharmacology
    Document Type
    Journal Article
    Publication Date
    2019-11-14
    Keywords
    Adaptive immunity
    Allergy
    Autoimmunity
    Immunology
    T cells
    Amino Acids, Peptides, and Proteins
    Biochemical Phenomena, Metabolism, and Nutrition
    Biochemistry
    Enzymes and Coenzymes
    Immune System Diseases
    Immunity
    Immunopathology
    Immunoprophylaxis and Therapy
    Musculoskeletal Diseases
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    Link to Full Text
    https://doi.org/10.1172/jci.insight.129687
    Abstract
    Dysregulated citrullination, a unique form of posttranslational modification catalyzed by the peptidylarginine deiminases (PADs), has been observed in several human diseases, including rheumatoid arthritis. However, the physiological roles of PADs in the immune system are still poorly understood. Here, we report that global inhibition of citrullination enhances the differentiation of type 2 helper T (Th2) cells but attenuates the differentiation of Th17 cells, thereby increasing the susceptibility to allergic airway inflammation. This effect on Th cells is due to inhibition of PAD2 but not PAD4. Mechanistically, PAD2 directly citrullinates GATA3 and RORgammat, 2 key transcription factors determining the fate of differentiating Th cells. Citrullination of R330 of GATA3 weakens its DNA binding ability, whereas citrullination of 4 arginine residues of RORgammat strengthens its DNA binding. Finally, PAD2-deficient mice also display altered Th2/Th17 immune response and heightened sensitivity to allergic airway inflammation. Thus, our data highlight the potential and caveat of PAD2 as a therapeutic target of Th cell-mediated diseases.
    Source

    JCI Insight. 2019 Nov 14;4(22). pii: 129687. doi: 10.1172/jci.insight.129687. Link to article on publisher's site

    DOI
    10.1172/jci.insight.129687
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/41278
    PubMed ID
    31723060
    Related Resources

    Link to Article in PubMed

    ae974a485f413a2113503eed53cd6c53
    10.1172/jci.insight.129687
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    UMass Chan Faculty and Researcher Publications
    Thompson Lab Publications

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