<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Zohar, Yaniv</dc:creator>
  <dc:creator>Wildbaum, Gizi</dc:creator>
  <dc:creator>Novak, Rostislav</dc:creator>
  <dc:creator>Salzman, Andrew L.</dc:creator>
  <dc:creator>Thelen, Marcus</dc:creator>
  <dc:creator>Alon, Ronen</dc:creator>
  <dc:creator>Barsheshet, Yiftah</dc:creator>
  <dc:creator>Karp, Christopher L.</dc:creator>
  <dc:creator>Karin, Nathan</dc:creator>
  <dc:date>2014-04-08</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">A single G protein–coupled receptor (GPCR) can activate multiple signaling cascades  based on the binding of different ligands. The biological relevance of this feature in  immune regulation has not been evaluated. The chemokine-binding GPCR CXCR3 is  preferentially expressed on CD4+ T cells, and canonically binds 3 structurally related  chemokines: CXCL9, CXCL10, and CXCL11. Here we have shown that CXCL10/CXCR3  interactions drive effector Th1 polarization via STAT1, STAT4, and STAT5  phosphorylation, while CXCL11/CXCR3 binding induces an immunotolerizing state that is  characterized by IL-10hi (Tr1) and IL-4hi (Th2) cells, mediated via p70 kinase/mTOR in  STAT3- and STAT6-dependent pathways. CXCL11 binds CXCR3 with a higher affinity  than CXCL10, suggesting that CXCL11 has the potential to restrain inflammatory  autoimmunity. We generated a CXCL11-Ig fusion molecule and evaluated its use in the  EAE model of inflammatory autoimmune disease. Administration of CXCL11-Ig during the  first episode of relapsing EAE in SJL/J mice not only led to rapid remission, but also  prevented subsequent relapse. Using GFP-expressing effector CD4+ T cells, we  observed that successful therapy was associated with reduced accumulation of these  cells at the autoimmune site. Finally, we showed that very low doses of CXCL11 rapidly  suppress signs of EAE in C57BL/6 mice lacking functional CXCL11.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://susi.usi.ch/global/documents/318977</dc:identifier>
  <dc:identifier>https://n2t.net/ark:/12658/srd1318977</dc:identifier>
  <dc:identifier>https://susi.usi.ch/documents/318977/files/Zohar_JCI_2014.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1172/JCI71951</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/ark/12658/srd1318977</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>License undefined</dc:rights>
  <dc:source>The journal of clinical investigation. - 2014, vol. 124, no. 5, p. 2009-2022</dc:source>
  <dc:subject>info:eu-repo/classification/udc/57</dc:subject>
  <dc:title xmlns:ns1="xml" ns1:lang="en">CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>