Foxp3 phosphorylation

Foxp3 drives oxidative phosphorylation and protection from lipotoxicity.

Tregs can adopt a catabolic metabolic program with increased capacity for fatty acid oxidation-fueled oxidative phosphorylation (OXPHOS). It is unclear why this form of metabolism is favored in Tregs and, more specifically, whether this program represents an adaptation to the environment and developmental cues or is "hardwired" by Foxp3. Here we show, using metabolic analysis and an unbiased ma...

Phosphorylation of FOXP3 by LCK Downregulates MMP9 Expression and Represses Cell Invasion

Forkhead Box P3 (FOXP3) is a member of the forkhead/winged helix family of the transcription factors and plays an important role not only as a master gene in T-regulatory cells, but also as a tumor suppressor. In this study, we identified lymphocyte-specific protein tyrosine kinase (LCK), which correlates with cancer malignancy, as a binding partner of FOXP3. FOXP3 downregulated LCK-induced MMP...

Promiscuous Foxp3-cre activity reveals a differential requirement for CD28 in Foxp3+ and Foxp3− T cells

Costimulatory signals by CD28 are critical for thymic regulatory T-cell (Treg) development. To determine the functional relevance of CD28 for peripheral Treg post thymic selection, we crossed the widely used Forkhead box protein 3 (Foxp3)-CreYFP mice to mice bearing a conditional Cd28 allele. Treg-specific CD28 deficiency provoked a severe autoimmune syndrome as a result of a strong disadvantag...

Regulation of Foxp3

Functional analysis of FOXP3.

Tolerance to self antigens is established in two ways: first in the thymus through the deletion of thymocytes expressing self-reactive T cell receptors; and second, in the periphery through multiple mechanisms involving deletion, anergy, and suppression. Dominant tolerance to self antigens in the periphery is primarily the function of the CD4(+)CD25(+)FOXP3(+) subset of T cells, which have the ...