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J Immunol. 2013 May 1;190(9):4470-3. doi: 10.4049/jimmunol.1203561. Epub 2013 Mar 29.

Cutting Edge: a novel, human-specific interacting protein couples FOXP3 to a chromatin-remodeling complex that contains KAP1/TRIM28.

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  • 1Immunology Research Program, Benaroya Research Institute, Seattle, WA 98101, USA.


Regulatory T cells (Tregs) play a pivotal role in the maintenance of immunological self-tolerance. Deficiency or dysfunction of Tregs leads to severe autoimmune diseases. Although the forkhead/winged-helix family member FOXP3 is critical for Treg differentiation and function, the molecular basis for FOXP3 function remains unclear. In this study, we identified and characterized a human-specific FOXP3-interacting protein, referred to as FIK (FOXP3-interacting KRAB domain-containing protein). FIK is highly expressed in Tregs and acts as a bridging molecule to link FOXP3 with the chromatin-remodeling scaffold protein KAP1 (TIF-1β/TRIM28). Disruption of the FOXP3-FIK-KAP1 complex in Tregs restored expression of FOXP3-target genes and abrogated the suppressor activity of the Tregs. These data demonstrate a critical role for FIK in regulating FOXP3 activity and Treg function.

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