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PGRN also has potent anti-inflammatory functionality and deregulated PGRN is associated with rheumatoid arthritis and inflammatory bowel disease. We have previously reported that PGRN directly binds to TNFR and significantly enhances T<jats:sub>reg<\/jats:sub> population and stimulatesIL-10 production. To further investigate PGRN\u2019s function in the immune system we performed a gene array analysis on CD4+ T cells from wild type B6 mice and PGRN \u2212\/\u2212 mice. We identified many chemokines and their receptors, among which CXCL9 and CXCL10 were most prominent, that were significantly induced in PGRN null mice. Administration of recombinant PGRN protein strongly inhibited TNF and IFN-\u03b3-induced CXCL9 and CXCL10 expression. In addition, CXCL9 expression is strongly upregulated in PGRN KO mice and its level is correlated with severity of inflammation in a dermatitis model. Further, we have demonstrated that PGRN-mediated inhibition of chemokine expression largely depends on TNFR1. Taken together, this study provides new insights into the mechanisms underlying PGRN mediated regulation of various inflammatory and autoimmune diseases.<\/jats:p>","DOI":"10.1038\/srep21115","type":"journal-article","created":{"date-parts":[[2016,2,19]],"date-time":"2016-02-19T10:19:56Z","timestamp":1455877196000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Progranulin inhibits expression and release of chemokines CXCL9 and CXCL10 in a TNFR1 dependent manner"],"prefix":"10.1038","volume":"6","author":[{"given":"Jyoti Joshi","family":"Mundra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Jian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyal","family":"Bhagat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-ju","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,19]]},"reference":[{"key":"BFsrep21115_CR1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nm816","volume":"9","author":"Z He","year":"2003","unstructured":"He, Z., Ong, C. 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