Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis

Abstract

The roles of neutrophils in renal inflammation are currently unclear. On examining these cells in the unilateral ureteral obstruction murine model of chronic kidney disease, we found that the injured kidney bore a large and rapidly expanding population of neutrophils that expressed the eosinophil marker Siglec-F. We first verified that these cells were neutrophils. Siglec-F + neutrophils were recently detected in several studies in other disease contexts. We then showed that a) these cells were derived from conventional neutrophils in the renal vasculature by TGF-β1 and GM-CSF; b) they differed from their parent cells by more frequent hypersegmentation, higher expression of profibrotic inflammatory cytokines, and notably, expression of collagen 1; and c) their depletion reduced collagen deposition and disease progression, but adoptive transfer increased renal fibrosis. These findings have thus unveiled a subtype of neutrophils that participate in renal fibrosis and a potentially new therapeutic target in chronic kidney disease.

RAGE contributes to allergen driven severe neutrophilic airway inflammation via NLRP3 inflammasome activation in mice

“…Moreover Siglec8+ (human homolog to murine SiglecF) were increased in patients with Asthma-COPD overlap. Other studies have reported that SiglecF+ neutrophils have a prolonged lifespan, hypersegmented nuclei, increased mobility and an enhanced inflammatory phenotype ( 67 – 71 ). The current study also found that SiglecF+ neutrophils were present in the airways along with NET accumulation after AA exposure.…”

Deficiency of leukotriene B4 receptor type 1 ameliorates ovalbumin‐induced allergic enteritis in mice

“…In addition, LTB4/BLT1 has been reported to contribute to neutrophil, eosinophil, helper T‐cell and dendritic cell chemotaxis 14,29,30 . Although CD170, also known as Siglec‐F, is a widely used eosinophil marker in mice, 31,32 some subsets of neutrophils also express Siglec‐F 33,34 . Therefore, it is possible that some CD170+ cells are neutrophils.…”

The neutrophil: A key resourceful agent in immune‐mediated vasculitis

“…In the same study, single‐cell transcriptomic analysis was used to distinguish specific sub‐populations of neutrophils without providing their precise phenotypic characterization. Finally, a murine model of renal fibrosis showed that a new Siglec‐F‐expressing neutrophil subtype promoted collagen I production by fibroblasts 352 . Siglec‐F‐positive neutrophils were also able to produce collagen I directly.…”