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

J Clin Invest. 2022 Jun 15;132(12):e156876. doi: 10.1172/JCI156876.


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.

Keywords: Chronic kidney disease; Fibrosis; Immunology; Nephrology; Neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen / metabolism
  • Fibrosis
  • Kidney / metabolism
  • Kidney Diseases* / metabolism
  • Mice
  • Neutrophils / metabolism
  • Renal Insufficiency, Chronic* / metabolism
  • Sialic Acid Binding Immunoglobulin-like Lectins / metabolism*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Ureteral Obstruction* / genetics
  • Ureteral Obstruction* / metabolism
  • Ureteral Obstruction* / pathology


  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Siglecf protein, mouse
  • Transforming Growth Factor beta1
  • Collagen