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Regulating immune regulators

Jul. 17, 2014, 8:00 AM

Regulatory T cells (Tregs) are a specialized subset of T cells that maintain self-tolerance and prevent autoimmunity. They are composed of thymus-derived (tTregs) and peripheral-derived (pTregs) cells; however, the signaling events that control development of these two populations are not well defined.

For the first time, Sudheer Pabbisetty, Ph.D., Eric Sebzda, Ph.D., and colleagues identify a transcription factor (KLF2) that is specifically required for the generation of pTregs but not tTregs. They also show that drugs that stabilize KLF2 protein levels enhance pTreg development.

The findings, published in the July 1 Proceedings of the National Academy of Sciences, indicate that KLF2 is a therapeutic target for controlling Treg production. While increasing Tregs is valuable in limiting autoimmunity, it can be detrimental in situations where Tregs hinder desired immune responses – such as those directed against tumors. In these cases, it might be desirable to use drugs that promote KLF2 degradation to reduce the production of Tregs.

This research was supported by a grant from the National Institutes of Health (HL094773).

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