{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:58:10Z","timestamp":1779296290442,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR056099"],"award-info":[{"award-number":["AR056099"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AR065778"],"award-info":[{"award-number":["AR065778"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI147697"],"award-info":[{"award-number":["AI147697"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003185","name":"National Psoriasis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003185","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Thirty percent of psoriasis patients develop psoriatic arthritis (PsA), nevertheless the mechanism remains unknown. Endogenous GU\u2010rich miRNAs activate endosomal TLR7 that plays a critical role in autoimmune diseases. We found that endogenous TLR7 ligands, miR\u201029 and miR\u2010Let7b, were markedly increased in PsA compared to osteoarthritis (OA) synovial fluid (SF)s. We showed that intradermal (i.d.) miR\u2010Let7b injection promoted skin inflammation, which was characterized by amplified Th1 cells, CD68\n                    <jats:sup>+<\/jats:sup>\n                    M1 macrophages, and transcriptional upregulation of glycolytic mediators, GLUT1, C\u2010MYC, and HIF1\u03b1. Expansion of skin Th1 cells driven by miR\u2010Let7b was also linked to elevated M1\u2010associated IRFs. Interestingly, i.d. miR\u2010Let7b administration exacerbated suboptimal joint inflammation along with metabolic reconfiguration of the PsA\u2010like preclinical model. Moreover, TLR7 agonist, R837, potentiated metabolic reprogramming and expression of IL\u20101\u03b2, IL\u20106, and IL\u201012 in murine macrophages, enabling myeloid\u2010to\u2010T\u2010cell crosstalk. Consistently, treatment with glycolytic inhibitors, 2\u2010DG and\/or HIF1\u03b1i, reversed R837\u2010induced metabolic remodeling and disrupted the TLR7\u2010driven inflammatory phenotype in myeloid and lymphoid cells. Similar to miR\u2010Let7b, R837 also differentiates progenitor cells into mature osteoclasts, primarily through RANKL induction. Taken together, this study indicates that TLR7\u2010instigated metabolic rewiring of macrophages and their cross\u2010regulation of T cells connects skin immunopathology to joint inflammation.\n                  <\/jats:p>","DOI":"10.1002\/eji.202048690","type":"journal-article","created":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T11:08:21Z","timestamp":1603192101000},"page":"714-720","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["TLR7 endogenous ligands remodel glycolytic macrophages and trigger skin\u2010to\u2010joint crosstalk in psoriatic arthritis"],"prefix":"10.1002","volume":"51","author":[{"given":"Katrien","family":"Van Raemdonck","sequence":"first","affiliation":[{"name":"Jesse Brown VA Medical Center Chicago IL USA"},{"name":"Department of Medicine Division of Rheumatology University of Illinois at Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-5751","authenticated-orcid":false,"given":"Sadiq","family":"Umar","sequence":"additional","affiliation":[{"name":"Jesse Brown VA Medical Center Chicago IL USA"},{"name":"Department of Medicine Division of Rheumatology University of Illinois at Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karol","family":"Palasiewicz","sequence":"additional","affiliation":[{"name":"Jesse Brown VA Medical Center Chicago IL USA"},{"name":"Department of Medicine Division of Rheumatology University of Illinois at Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Romay","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Rheumatology University of Illinois at Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suncica","family":"Volkov","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Rheumatology University of Illinois at Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiva","family":"Arami","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Rheumatology University of Illinois at Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2215-0221","authenticated-orcid":false,"given":"Nadera","family":"Sweiss","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Rheumatology University of Illinois at Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6698-8491","authenticated-orcid":false,"given":"Shiva","family":"Shahrara","sequence":"additional","affiliation":[{"name":"Jesse Brown VA Medical Center Chicago IL USA"},{"name":"Department of Medicine Division of Rheumatology University of Illinois at Chicago Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2016.12.003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39544"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-201203"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13520"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3008089"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802999"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343801"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.16203"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1987.tb05785.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1483"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02191"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00053"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.123047"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2017.04.010"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8020020"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.119.263657"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.08.043"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.13850"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00015"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","first-page":"706","DOI":"10.14348\/molcells.2017.0225","article-title":"Current understanding of RANK signaling in osteoclast differentiation and maturation","volume":"40","author":"Park J. 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