T-cell-intrinsic Tif1[Alpha]/Trim24 regulates IL-1R expression on T^sub H^2 cells and T^sub H^2 cell-mediated airway allergy

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 ...CD4+ T-helper 2 (T...2) cells orchestrate the type-2-driven immune response in a large proportion of atopic asthmatics. To identify previously unidentified putative targets in pathogenic T...2 cells, we performed in silico analyses of recently published transcriptional data from a wide variety of pathogenic T... cells [Okoye IS, et al. (2014) Proc Natl Acad Sci USA 111(30):E3081-E3090] and identified that transcription intermediary factor 1 regulator-alpha (Tif1...)/tripartite motif-containing 24 (Trim24) was predicted to be active in house dust mite (HDM)- and helminth-elicited Il4...CD4+ T...2 cells but not in T..., T...17, 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 T...2 cytokines and chemokines and were predicted to have compromised IL-1-regulated signaling. Following this prediction, we found that Trim24-/- T cells have reduced IL-1 receptor (IL-1R) expression, are refractory to IL-1...-mediated activation in vitro and in vivo, and fail to respond to IL-1...-exacerbated airway allergy. Collectively, these data identify a previously unappreciated Trim24-dependent requirement for IL-1R expression on T...2 cells and an important nonredundant role for T-cell-intrinsic Trim24 in T...2-mediated allergy and antihelminth immunity. (ProQuest: ... denotes formulae/symbols omitted.)