Editors' ChoiceImmunology

New connections: Restoring immune balance

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Science Signaling  08 Dec 2020:
Vol. 13, Issue 661, eabf9854
DOI: 10.1126/scisignal.abf9854

New targets to expand regulatory T cell populations may be therapeutic for autoimmune and inflammatory diseases.

Regulatory T (Treg) cells act as critical suppressors of immune system activity by repressing effector T (Teff) cells. In patients with autoimmune and chronic inflammatory diseases, increasing the number and activity of Treg cells may be therapeutically beneficial. Two studies in this issue of Science Signaling uncover targets and a potential antibody that might be developed further for that purpose. Mendu et al. found that blocking the channel and kinase TRPM7 increases the number of Treg cells in mice. Loss of TRPM7 in mice increased T cell sensitivity and response to the cytokine IL-2, promoted Treg cell development in the thymus, and was protective against Teff cell–dependent hepatitis. Therefore, targeting TRPM7 may be a way to increase Treg cell numbers in patients. Treg cells are stimulated by ligands that activate the cytokine receptor TNFR2. Torrey et al. developed an antibody that stimulates TNFR2 and triggers the proliferation and activation of immunosuppressive Treg cells. Applying the TNFR2 agonist antibody to cultures of primary human T cells resulted in an increase in the number of Treg cells and, hence, the repression of Teff cells. Various features of the antibody suggested it may even be more potent and, critically, less toxic than current methods of activating Treg cells. The findings from these papers reveal new insights and tools with which the balance between Treg and Teff cells may be restored to treat inflammatory disease.

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