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.
CITATION STYLE
Kassianos, A. J., Wang, X., Sampangi, S., Afrin, S., Wilkinson, R., & Healy, H. (2015). Fractalkine-CX3CR1-dependent recruitment and retention of human CD1c + myeloid dendritic cells by in vitro-activated proximal tubular epithelial cells. Kidney International, 87(6), 1153–1163. https://doi.org/10.1038/ki.2014.407
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