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To dissect the function of CCR5 in acute and chronic renal allograft rejection, bilaterally nephrectomized WT and <jats:italic>Ccr5<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> C57BL\/6 mice were used as recipients of WT BALB\/c renal allografts and analyzed 7 and 42 days after transplantation. Lesion scores (glomerular damage, vascular rejection, tubulointerstitial inflammation) and numbers of CD4<jats:sup>+<\/jats:sup>, CD8<jats:sup>+<\/jats:sup>, CD11c<jats:sup>+<\/jats:sup> and alpha smooth muscle actin (\u03b1SMA)<jats:sup>+<\/jats:sup> cells were reduced in allografts from <jats:italic>Ccr5<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> recipients during the chronic phase. Increasing creatinine levels indicated deterioration of allograft function over time. While mRNA expression of Th1\u2010associated markers decreased between 7 and 42 days, Th2\u2010associated markers increased. Markers for alternatively activated macrophages (arginase 1, chitinase 3\u2010like 3, resistin\u2010like \u03b1, mannose receptor, C type 1), were strongly upregulated (mRNA and\/or protein level) only in allografts from <jats:italic>Ccr5<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> recipients at 42 days. <jats:italic>Ccr5<\/jats:italic> deficiency shifted intragraft immune responses during the chronic phase towards the Th2 type and led to accumulation of alternatively activated macrophages. Additionally, splenocytes from unchallenged <jats:italic>Ccr5<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice showed significantly increased arginase 1 and mannose receptor 1 mRNA levels, suggesting constitutive alternative activation of splenic macrophages. We conclude that <jats:italic>Ccr5<\/jats:italic> deficiency favors alternative macrophage activation. This finding may be relevant for other inflammatory diseases that involve macrophage activation and may also influence future therapeutic strategies targeting CCR5.<\/jats:p>","DOI":"10.1002\/eji.200939652","type":"journal-article","created":{"date-parts":[[2009,10,14]],"date-time":"2009-10-14T17:53:27Z","timestamp":1255542807000},"page":"267-278","source":"Crossref","is-referenced-by-count":36,"title":["Chemokine receptor <i>Ccr5<\/i> deficiency induces alternative macrophage activation and improves long\u2010term renal allograft outcome"],"prefix":"10.1002","volume":"40","author":[{"given":"Stefan","family":"Dehmel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Kiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Loewe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Chilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlef","family":"Schl\u00f6ndorff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann\u2010Josef","family":"Gr\u00f6ne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Luckow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,12,30]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.22.012703.104543"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1275"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00118-2"},{"key":"e_1_2_6_5_2","first-page":"343","article-title":"Chemokine receptors and transplantation","volume":"2","author":"Tan J.","year":"2005","journal-title":"Cell. 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