{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T21:55:40Z","timestamp":1791064540091,"version":"4.1.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Renal pathology in systemic lupus erythematosus involves both autoantibody deposition and a cellular inflammatory response, both of which are mediated by effector CD4 T cells. MRLlpr mice spontaneously develop massive perivascular infiltrates, but the pathways that regulate the development, trafficking, and effector functions of kidney-infiltrating T cells are poorly defined. To address these questions, we first surveyed inflammatory chemokine protein levels in nephritic kidneys from lupus-prone MRLlpr mice. After identifying highly elevated levels of the CXCR3 ligand CXCL9, we found that kidney-infiltrating effectors are enriched for expression of CXCR3, as well as P-selectin ligand and ICOS. Using genetic ablation, we demonstrate that ICOS plays an essential role in the establishment of renal perivascular infiltrates, although a small number of infiltrating cells remain around the blood vessels. Interestingly, though IgG autoantibody production is substantially reduced in Icos\u2212\/\u2212 MRLlpr mice, the progression of immune complex glomerulonephritis is only modestly diminished and the production of inflammatory chemokines, such as CXCL9, remains high in the kidney. We find that Icos\u2212\/\u2212 effector cell numbers are only slightly reduced and these have normal expression of CXCR3 and P-selectin ligand with intact migration to CXCL9. However, they have impaired production of inflammatory cytokines and fail to show evidence of efficient proliferation in the kidney. Thus, while dispensable for acquisition of renal trafficking receptor expression, ICOS is strictly required for local inflammatory functions of autoreactive CD4 T cells in murine lupus.<\/jats:p>","DOI":"10.4049\/jimmunol.0800758","type":"journal-article","created":{"date-parts":[[2009,3,19]],"date-time":"2009-03-19T20:57:19Z","timestamp":1237496239000},"page":"4076-4084","source":"Crossref","is-referenced-by-count":41,"title":["ICOS Controls Effector Function but Not Trafficking Receptor Expression of Kidney-Infiltrating Effector T Cells in Murine Lupus"],"prefix":"10.1093","volume":"182","author":[{"given":"Jared M","family":"Odegard","sequence":"first","affiliation":[{"name":"Department of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah D","family":"DiPlacido","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lark","family":"Greenwald","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kashgarian","sequence":"additional","affiliation":[{"name":"Department of Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight H","family":"Kono","sequence":"additional","affiliation":[{"name":"Department of Immunology & Microbial Sciences, The Scripps Research Institute , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Flavell","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"},{"name":"Howard Hughes Medical Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Craft","sequence":"additional","affiliation":[{"name":"Department of Immunobiology"},{"name":"Department of Internal Medicine, Section of Rheumatology, Yale School of Medicine , New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,4,1]]},"reference":[{"key":"2025032622383514500_R1","first-page":"162","article-title":"Affinity between the lupus erythematosus serum factor and cell nuclei and nucleoprotein.","volume-title":"Science","year":"1957"},{"key":"2025032622383514500_R2","first-page":"303","article-title":"Systemic lupus erythematosus.","volume-title":"Cell","year":"1996"},{"key":"2025032622383514500_R3","first-page":"1137","article-title":"Prevention of nephritis in major histocompatibility complex class II-deficient MRL-lpr mice.","volume-title":"J. 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Immunol.","year":"2001"},{"key":"2025032622383514500_R33","first-page":"605","article-title":"The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE.","volume-title":"Nat. Immunol.","year":"2001"},{"key":"2025032622383514500_R34","first-page":"97","article-title":"ICOS co-stimulatory receptor is essential for T-cell activation and function.","volume-title":"Nature","year":"2001"},{"key":"2025032622383514500_R35","first-page":"696","article-title":"Loci predisposing to autoimmunity in MRL-Faslpr and C57BL\/6-Faslpr mice.","volume-title":"J. Clin. 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