The enemy within_ endogenous retroelements and autoimmune disease.英文文献资料.pdf

NIH Public Access Author Manuscript Nat Immunol . Author manuscript; available in PMC 2014 November 01. N Published in final edited form as: I H Nat Immunol . 2014 May ; 15(5): 415–422. doi:10.1038/ni.2872. - P A A u The enemy within: endogenous retroelements and autoimmune t h o r disease M a n 1 1,* Hannah E. Volkman and Daniel B. Stetson u s 1 c Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109 r i p USA t Abstract Inappropriate or chronic detection of self nucleic acids by the innate immune system underlies a number of human autoimmune diseases. We discuss here an unexpected source of endogenous immunostimulatory nucleic acids: the reverse transcribed cDNAs of endogenous retroelements. N The interplay between innate immune sensing and clearance of retroelement cDNAs has important I H - implications for understanding immune responses to infectious retroviruses like human P A immunodeficiency virus (HIV). Further, cDNA detection by the innate immune system reveals an A evolutionary tradeoff: selection for a vigorous, sensitive response to infectious retroviruses may u t h predispose to inappropriate detection of endogenous retroelements. We propose that this tradeoff o r has placed unique constraints on the sensitivity of the DNA-activated antiviral response, with M implications for the interactions of DNA viruses and retroviruses with their hosts. Finally, we a n u discuss how a be