Induction of Systemic Autoimmunity by a Xenobiotic Requires Endosomal TLR Trafficking and Signaling from the Late Endosome and Endolysosome but Not Type I IFN

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Fältnamn	Indikatorer	Metadata
000		04040naa a2200457 4500
001		oai:DiVA.org:liu-143622
003		SwePub
008		171213s2017 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-1436222 URI
024	7	a https://doi.org/10.4049/jimmunol.17003322 DOI
040		a (SwePub)liu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Pollard, K. Michaelu Scripps Research Institute, CA 92037 USA4 aut
245	1 0	a Induction of Systemic Autoimmunity by a Xenobiotic Requires Endosomal TLR Trafficking and Signaling from the Late Endosome and Endolysosome but Not Type I IFN
264		c 2017-12-01
264	1	b AMER ASSOC IMMUNOLOGISTS,c 2017
338		a print2 rdacarrier
500		a Funding Agencies\|National Institutes of Health [ES007511, ES021464, ES022625, HL114408]
520		a Type I IFN and nucleic acid-sensing TLRs are both strongly implicated in the pathogenesis of lupus, with most patients expressing IFN-induced genes in peripheral blood cells and with TLRs promoting type I IFNs and autoreactive B cells. About a third of systemic lupus erythematosus patients, however, lack the IFN signature, suggesting the possibility of type I IFN-independent mechanisms. In this study, we examined the role of type I IFN and TLR trafficking and signaling in xenobiotic systemic mercury-induced autoimmunity (HgIA). Strikingly, autoantibody production in HgIA was not dependent on the type I IFN receptor even in NZB mice that require type I IFN signaling for spontaneous disease, but was dependent on the endosomal TLR transporter UNC93B1 and the endosomal proton transporter, solute carrier family 15, member 4. HgIA also required the adaptor protein-3 complex, which transports TLRs from the early endosome to the late endolysosomal compartments. Examination of TLR signaling pathways implicated the canonical NF-kappa B pathway and the proinflammatory cytokine IL-6 in autoantibody production, but not IFN regulatory factor 7. These findings identify HgIA as a novel type I IFN-independent model of systemic autoimmunity and implicate TLR-mediated NF-kappa B proinflammatory signaling from the late endocytic pathway compartments in autoantibody generation.
650	7	a NATURVETENSKAPx Biologix Immunologi0 (SwePub)106052 hsv//swe
650	7	a NATURAL SCIENCESx Biological Sciencesx Immunology0 (SwePub)106052 hsv//eng
700	1	a Escalante, Gabriela M.u Scripps Research Institute, CA 92037 USA4 aut
700	1	a Huang, Huau Scripps Research Institute, CA 92037 USA4 aut
700	1	a Haraldsson, Katarina M.u Scripps Research Institute, CA 92037 USA4 aut
700	1	a Hultman, Peru Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Region Östergötland, Klinisk patologi4 aut0 (Swepub:liu)perhu66
700	1	a Christy, Joseph M.u Scripps Research Institute, CA 92037 USA4 aut
700	1	a Pawar, Rahul D.u Scripps Research Institute, CA 92037 USA4 aut
700	1	a Mayeux, Jessica M.u Scripps Research Institute, CA 92037 USA4 aut
700	1	a Gonzalez-Quintial, Rosanau Scripps Research Institute, CA 92037 USA4 aut
700	1	a Baccala, Robertou Scripps Research Institute, CA 92037 USA4 aut
700	1	a Beutler, Bruceu University of Texas Southwestern Medical Centre Dallas, USA4 aut
700	1	a Theofilopoulos, Argyrios N.u Scripps Research Institute, CA 92037 USA4 aut
700	1	a Kono, Dwight H.u Scripps Research Institute, CA 92037 USA4 aut
710	2	a Scripps Research Institute, CA 92037 USAb Avdelningen för neuro- och inflammationsvetenskap4 org
773	0	t Journal of Immunologyd : AMER ASSOC IMMUNOLOGISTSg 199:11, s. 3739-3747q 199:11<3739-3747x 0022-1767x 1550-6606
856	4	u https://www.jimmunol.org/content/jimmunol/199/11/3739.full.pdf
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-143622
856	4 8	u https://doi.org/10.4049/jimmunol.1700332

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Av författaren/redakt...: Pollard, K. Mich ...; Escalante, Gabri ...; Huang, Hua; Haraldsson, Kata ...; Hultman, Per; Christy, Joseph ...; visa fler...; Pawar, Rahul D.; Mayeux, Jessica ...; Gonzalez-Quintia ...; Baccala, Roberto; Beutler, Bruce; Theofilopoulos, ...; Kono, Dwight H.; visa färre...

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