Research ArticleAUTOIMMUNITY

Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions

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Science Immunology  16 Jun 2017:
Vol. 2, Issue 12, eaai9297
DOI: 10.1126/sciimmunol.aai9297

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TIPing the balance of autoimmunity

Individuals with mutations in Foxp3 develop an autoimmune syndrome called immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX). However, the severity of IPEX varies depending on the specific Foxp3 mutation. Now, Bin Dhuban et al. find that the most common IPEX mutation, p.A384T, disrupts FOXP3 binding to the histone acetyltransferase TIP60 (KAT5), resulting in abrogated regulatory T (Treg) cell suppressive capacity, but maintained repression of proliferation and inflammatory cytokine production. Allosteric modifiers that help stabilize TIP60-FOXP3 interactions by inhibiting the autoacetylation of TIP60 molecules correct this disruption. These data suggest that targeting this interaction may be a therapeutic avenue in treating IPEX and other autoimmune and inflammatory diseases.