LKB1 helps Treg cells battle exhaustion

Cully, Megan

doi:10.1038/nrd.2017.188

Research Highlight
Published: 22 September 2017

Autoimmune disease

LKB1 helps T_reg cells battle exhaustion

Megan Cully

Nature Reviews Drug Discovery volume 16, page 680 (2017)Cite this article

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In this article, mice in which the gene encoding LKB1 was deleted in T_reg cells (Foxp3^creStk11^fl/fl mice) had short lifespans, low body weight, skin ulcers and inflammatory manifestations including splenomegaly, lymphadenopathy and immune cell infiltration of multiple organs that led to a fatal autoimmune disease. This phenotype was associated with high levels of T helper 2 (T_H2) cytokines — interleukin-4 (IL-4) and IL-5 — present in the serum and secreted by T_eff cells.

T_reg cell numbers were reduced in Foxp3^creStk11^fl/fl mice and these cells expressed high levels of apoptotic markers. Depletion of the pro-apoptotic protein BIM largely restored T_reg cell numbers but did not restore T_eff cell numbers, suggesting that LKB1 affects T_reg cell apoptosis and function through independent mechanisms.

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References

Yang, K. et al. Homeostatic control of metabolic and functional fitness of Treg cells by LKB1 signalling. Nature 548, 602–606 (2017)
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