The immunologic X-factor

The liver X receptor β (LXRβ) is a nuclear receptor that plays a key role in the regulation of lipid and cholesterol metabolism and inflammatory immune responses. Yet its precise role in T cell biology has thus far been unclear. In a December Brief Definitive Report in the Journal of Experimental Medicine, a team led by Ludwig MSK’s Alexander Rudensky and Clarissa Campbell revealed that the loss of LXRβ in a mouse model leads to a severe deficiency of T cells accompanied by the spontaneous activation of effector T cells. Studies of chimeric mice with mixed populations of LXRβ-deficient T cells and normal T cells showed that the receptor is needed for T cell fitness, and that its loss especially compromises regulatory T cells (Tregs), which suppress effector T cells and protect tumors from anti-cancer immune responses. LXRβ deficiency, Alexander and his colleagues show, profoundly compromises Treg function. Indeed, the loss of just one copy of the LXRβ gene in Tregs suffices to induce early and fatal autoimmune disease in mice. The researchers argue these findings suggest the receptor could be a prime target for immunological therapies.

This article appeared in the April 2021 issue of Ludwig Link. Click here to download a PDF (1.4 MB).


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