English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Interleukin (IL)-17A signaling via Interleukin 17 receptor A ( Il17ra ) contributes to the inflammatory host response by inducing recruitment of innate immune cells, but also plays a role in homeostatic neutrophilic granulocyte regulation. Monocytes, the other main innate immune cell, have a longer life span and can pursue multiple differentiation pathways towards tissue macrophages. Monocytes are divided into two subpopulations by expression of the Ly6C/Gr1 surface marker in mice. We here investigated the role of  Il17ra  in monocyte homeostasis and macrophage generation. In  Il17ra -/-   and in mixed bone marrow chimeric wt/ Il17ra -/-   mice, the concentrations of circulating  Il17ra -/-  Gr1 low  monocytes were significantly decreased compared to wt cells. Pulmonary, splenic and resident peritoneal  Il17ra -/-   macrophages were significantly fewer than of wt origin. Bone marrow progenitor and monocyte numbers were equal, but the proportion of  Il17ra -/-  Gr1 low  monocytes was already decreased at bone marrow level. After monocyte depletion, initial Gr1 high  and Gr1 low  monocyte regeneration of  Il17ra -/-   and wt cells was very similar. However,  Il17ra -/-  Gr1 low  counts were not sustained. After labeling with either fluorescent beads or BrdU,  Il17ra -/-  Gr1 high  monocyte transition to Gr1 low  cells was not detectable unlike wt cells. Monocyte recruitment in acute peritonitis, which is known to be largely due to Gr1 high  cell migration, was unaffected in an identical environment. Unilateral ureteral obstruction induces a less acute inflammatory and fibrotic kidney injury. Compared to wt cells in the same environment,  Il17ra -/-   macrophage accumulation in the kidney was decreased. In the absence of  Il17ra  on all myeloid cells, renal fibrosis was significantly attenuated. Our data show that  Il17ra  modulates Gr1 low  monocyte counts and suggest defective Gr1 high  to Gr1 low  monocyte transition as an underlying mechanism. Lack of  Il17ra  altered homeostatic tissue macrophage formation and diminished renal inflammation and fibrosis.  Il17ra  appears to be a novel modulator of monocyte phenotype and possible therapeutic target in renal fibrosis.

Interleukin 17 Receptor A Modulates Monocyte Subsets and Macrophage Generation In Vivo