Role of perivascular cells in kidney homeostasis, inflammation, repair and fibrosis.

Perivascular niches in the kidney comprise heterogeneous cell populations, including pericytes and fibroblasts, with distinct functions. These perivascular cells have crucial roles in preserving kidney homeostasis as they maintain microvascular networks by stabilizing the vasculature and regulating capillary constriction. A subset of kidney perivascular cells can also produce and secrete erythropoietin; this ability can be enhanced with hypoxia-inducible factor-prolyl hydroxylase inhibitors, which are used to treat anaemia in chronic kidney disease.

Folic acid-mediated fibrosis is driven by C5a receptor 1-mediated activation of kidney myeloid cells.

We have previously reported that increased expression and activation of kidney cell complement components play an important role in the pathogenesis of renal scarring. Here, we used floxed green fluorescent protein (GFP)-C5a receptor 1 (C5aR1) knockin mice (GFP-) and the model of folic acid (FA)-induced kidney injury to define the cell types and potential mechanisms by which increased C5aR1 activation leads to fibrosis. Using flow cytometry and confocal microscopy, we identified macrophages as the major interstitial cell type showing increased expression of C5aR1 in FA-treated mice.

Autocrine vitamin D signaling switches off pro-inflammatory programs of T1 cells.

The molecular mechanisms governing orderly shutdown and retraction of CD4 type 1 helper T (T1) cell responses remain poorly understood. Here we show that complement triggers contraction of T1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ T1 cells to suppressive interleukin-10 cells.