title: Fractalkine-CX3CR1-dependent recruitment and retention of human CD1c+ myeloid dendritic cells by in vitro-activated proximal tubular epithelial cells.
abstract: Chemokines play pivotal roles in tissue recruitment and retention of leukocytes, with CX3CR1 recently identified as a chemokine receptor that selectively targets mouse kidney dendritic cells (DCs). We have previously demonstrated increased tubulointerstitial recruitment of human transforming growth factor-β (TGF-β)-producing DCs in renal fibrosis and chronic kidney disease (CKD). However, little is known about the mechanism of human DC recruitment and retention within the renal interstitium. We identified CD1c+ DCs as the predominant source of profibrotic TGF-β and highest expressors of the fractalkine receptor CX3CR1 within the renal DC compartment. Immunohistochemical analysis of diseased human kidney biopsies showed colocalization of CD1c+ DCs with fractalkine-positive proximal tubular epithelial cells (PTECs). Human primary PTEC activation with interferon-γ and tumor necrosis factor-α induced both secreted and surface fractalkine expression. In line with this, we found fractalkine-dependent chemotaxis of CD1c+ DCs to supernatant from activated PTECs. Finally, in comparison with unactivated PTECs, we showed significantly increased adhesion of CD1c+ DCs to activated PTECs via a fractalkine-dependent mechanism. Thus, TGF-β-producing CD1c+ DCs are recruited and retained in the renal tubulointerstitium by PTEC-derived fractalkine. These cells are then positioned to play a role in the development of fibrosis and progression of chronic kidney disease.
authors.affiliation: 1] Conjoint Kidney Research Laboratory, Pathology Queensland, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia [2] Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia [3] Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Kassianos
authors.affiliation: 1] Conjoint Kidney Research Laboratory, Pathology Queensland, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia [2] Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Xiangju
authors.initials: X
authors.lastname: Wang
authors.affiliation: 1] Conjoint Kidney Research Laboratory, Pathology Queensland, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia [2] Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia [3] Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Sampangi
authors.affiliation: 1] Conjoint Kidney Research Laboratory, Pathology Queensland, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia [2] Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia [3] Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Sadia
authors.initials: S
authors.lastname: Afrin
authors.affiliation: 1] Conjoint Kidney Research Laboratory, Pathology Queensland, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia [2] Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia [3] Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia [4] Medical School, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Ray
authors.initials: R
authors.lastname: Wilkinson
authors.affiliation: 1] Conjoint Kidney Research Laboratory, Pathology Queensland, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia [2] Department of Renal Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Healy
mesh_terms: D000328:Adult; D000368:Aged; D018949:Antigens, CD1 / Q000032:analysis; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D002633:Chemotaxis; D003713:Dendritic Cells / Q000737:chemistry / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005355:Fibrosis / Q000503:physiopathology; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000737:chemistry / Q000502:physiology*; D019707:Receptors, Chemokine / Q000032:analysis / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018949:Antigens, CD1; C437944:CD1C protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D006023:Glycoproteins; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma