Limiting immune activation by “self” RNAs

The enzyme SKIV2L detects and destroys aberrant forms of cellular RNA before they can trigger potentially harmful immune responses according to a report published this week in Nature Immunology. These findings may have implications for autoimmune syndromes, such as lupus, associated with excessive type I interferon immune cell production.

Dan Stetson and colleagues show that the loss of the enzyme SKIV2L enhances RNA-mediated activation of cellular sensors that normally guard against RNA virus infection. SKIV2L-deficient cells are also more sensitive to a type of cellular stress called the unfolded protein response, which is often observed in highly secretory cells, such as those found in salivary glands. They find this stress produces aberrant “self” RNAs that likewise trigger the cellular RNA sensors, leading to the production of potent immune activators called type I interferons. This response, if unchecked, can lead to immunopathology. Pediatric patients with inherited deficiencies of SKIV2L likewise exhibit a strong “type I interferon signature”.

The authors speculate that certain autoimmune diseases, such as Sjogren’s syndrome and type I diabetes, may be linked to SKIV2L.