T-cell-intrinsic Tif1α/Trim24 regulates IL-1R expression on TH2 cells and TH2 cell-mediated airway allergy

Proceedings of the National Academy of Sciences of the United States of America
Jimena Perez-LloretMark S Wilson

Abstract

There is a paucity of new therapeutic targets to control allergic reactions and forestall the rising trend of allergic diseases. Although a variety of immune cells contribute to allergy, cytokine-secreting αβ(+)CD4(+) T-helper 2 (TH2) cells orchestrate the type-2-driven immune response in a large proportion of atopic asthmatics. To identify previously unidentified putative targets in pathogenic TH2 cells, we performed in silico analyses of recently published transcriptional data from a wide variety of pathogenic TH cells [Okoye IS, et al. (2014) Proc Natl Acad Sci USA 111(30):E3081-E3090] and identified that transcription intermediary factor 1 regulator-alpha (Tif1α)/tripartite motif-containing 24 (Trim24) was predicted to be active in house dust mite (HDM)- and helminth-elicited Il4(gfp+)αβ(+)CD4(+) TH2 cells but not in TH1, TH17, or Treg cells. Testing this prediction, we restricted Trim24 deficiency to T cells by using a mixed bone marrow chimera system and found that T-cell-intrinsic Trim24 is essential for HDM-mediated airway allergy and antihelminth immunity. Mechanistically, HDM-elicited Trim24(-/-) T cells have reduced expression of many TH2 cytokines and chemokines and were predicted to have compromised IL-1-regulated ...Continue Reading

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Citations

Aug 23, 2017·Vaccines·Sarah van TolRicardo Rajsbaum
Nov 7, 2018·International Journal of Rheumatic Diseases·Young KimJinhyun Kim
Aug 14, 2019·Future Virology·Girish Patil, Shitao Li
Sep 9, 2020·Annals of the Rheumatic Diseases·Jimin JeonYou-Sun Kim
Oct 30, 2020·Frontiers in Immunology·Wenyong YangHongbo Hu
Aug 28, 2021·International Journal of Molecular Sciences·Mahbuba AktherKwang-Ho Lee
Aug 29, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Joe Jongpyo LimJulia Yue Cui

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