title: Chemokine-mediated tissue recruitment of CXCR3+ CD4+ T cells plays a major role in the pathogenesis of chronic GVHD.
abstract: Chemokines regulate the migration of hemopoietic cells and play an important role in the pathogenesis of many immune-mediated diseases. Intradermal recruitment of CD8(+) T cells by CXCL10 is a central feature of the pathogenesis of cutaneous acute GVHD (aGVHD), but very little is known about the pathogenesis of chronic GVHD (cGVHD). Serum concentrations of the 3 CXCR3-binding chemokines, CXCL9, CXCL10, and CXCL11, were found to be markedly increased in patients with active cGVHD of the skin (n = 8). An 80% decrease in CD4(+) cells expressing CXCR3 was seen in the blood of these patients (n = 5), whereas CD4(+) cells were increased in tissue biopsies and were clustered around the central arterioles of the dermis. The well-documented increase in expression of CXCL10 in aGVHD therefore diversifies in cGVHD to include additional members of the CXCR3-binding family and leads to preferential recruitment of CD4(+) T cells. These observations reveal a central role for chemokine-mediated recruitment of CXCR3(+) T cells in cGVHD.
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham, United Kingdom. j.e.croudace@bham.ac.uk
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Croudace
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Inman
authors.forename: Ben E
authors.initials: BE
authors.lastname: Abbotts
authors.forename: Sandeep
authors.initials: S
authors.lastname: Nagra
authors.forename: Jane
authors.initials: J
authors.lastname: Nunnick
authors.forename: Prem
authors.initials: P
authors.lastname: Mahendra
authors.forename: Charles
authors.initials: C
authors.lastname: Craddock
authors.forename: Ram
authors.initials: R
authors.lastname: Malladi
authors.forename: Paul A H
authors.initials: PA
authors.lastname: Moss
mesh_terms: D000208:Acute Disease; D001160:Arterioles / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D054357:Chemokine CXCL10 / Q000097:blood / Q000502:physiology*; D054371:Chemokine CXCL11 / Q000097:blood / Q000502:physiology*; D054370:Chemokine CXCL9 / Q000097:blood / Q000502:physiology*; D002634:Chemotaxis, Leukocyte; D020405:Dermis / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D019337:Hematologic Neoplasms / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D054367:Receptors, CXCR3 / Q000502:physiology*; D019172:Transplantation Conditioning
chemical_list: C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D054367:Receptors, CXCR3