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Dry eye disease is the prominent ocular sequel of cGVHD and is caused by excessive inflammation and fibrosis in the lacrimal glands. Heavy chain-Hyaluronan\/Pentraxin 3 (HC-HA\/PTX3) is a complex purified from human amniotic membrane (AM) and known to exert anti-inflammatory and anti-scarring actions. In this study, we utilized a mouse model of cGVHD to examine whether HC-HA\/PTX3 could attenuate dry eye disease elicited by cGVHD. Our results indicated that subconjunctival and subcutaneous injection of HC-HA\/PTX3 preserved tear secretion and conjunctival goblet cell density and mitigated inflammation and scarring of the conjunctiva. Such therapeutic benefits were associated with suppression of scarring and infiltration of inflammatory\/immune cells in the lacrimal glands. Furthermore, HC-HA\/PTX3 significantly reduced the extent of infiltration of CD45<jats:sup>+<\/jats:sup> CD4<jats:sup>+<\/jats:sup> IL-17<jats:sup>+<\/jats:sup> cells, CD45<jats:sup>+<\/jats:sup> CD34<jats:sup>+<\/jats:sup> collagen I<jats:sup>+<\/jats:sup> CXCR4<jats:sup>+<\/jats:sup> fibrocytes, and HSP47<jats:sup>+<\/jats:sup> activated fibroblasts that were accompanied by upregulation of collagen type I\u03b11, collagen type III\u03b11 and NF-kB in lacrimal glands. Collectively, these pre-clinical data help prove the concept that subcutaneous and subconjunctival injection of HC-HA\/PTX3 is a novel approach to prevent dry eye disease caused by cGVHD and allow us to test its safety and efficacy in future human clinical trials.<\/jats:p>","DOI":"10.1038\/srep42195","type":"journal-article","created":{"date-parts":[[2017,2,6]],"date-time":"2017-02-06T10:08:31Z","timestamp":1486375711000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Heavy Chain-Hyaluronan\/Pentraxin 3 from Amniotic Membrane Suppresses Inflammation and Scarring in Murine Lacrimal Gland and Conjunctiva of Chronic Graft-versus-Host Disease"],"prefix":"10.1038","volume":"7","author":[{"given":"Yoko","family":"Ogawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Mukai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Imada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Wei","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megha","family":"Mahabole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scheffer C. 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