Sensing of RNA stress by mTORC1 drives autoinflammation

Sensing of RNA stress by mTORC1 drives autoinflammation

Blog Article

Loss-of-function mutations in SKIV2L underlie trichohepatoenteric syndrome (THES2), a rare inborn error of immunity characterized by diarrhea, skin lesions, brittle hair, and immunodeficiency.SKIV2L is part of a multiprotein complex required for exosome-mediated RNA surveillance through RNA decay.In this issue of the JCI, Yang et al.delineate a Mop Head mechanism underlying autoinflammatory skin disease in Skiv2l-deficient mice.Thus, a lack of SKIV2L activates mTORC1 signaling in keratinocytes and T cells, impeding skin barrier integrity and T cell homeostasis.

Interestingly, treatment with the mTOR inhibitor rapamycin DEODORANT FOREST improves skin symptoms in Skiv2l-deficient mice, suggesting a possible therapeutic avenue for patients with THES2.