Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis
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 ma...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2022-06-01
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| Series: | The Journal of Clinical Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/JCI156876 |
| _version_ | 1818236539132444672 |
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| author | Seungwon Ryu Jae Woo Shin Soie Kwon Jiwon Lee Yong Chul Kim Yoe-Sik Bae Yong-Soo Bae Dong Ki Kim Yon Su Kim Seung Hee Yang Hye Young Kim |
| author_facet | Seungwon Ryu Jae Woo Shin Soie Kwon Jiwon Lee Yong Chul Kim Yoe-Sik Bae Yong-Soo Bae Dong Ki Kim Yon Su Kim Seung Hee Yang Hye Young Kim |
| author_sort | Seungwon Ryu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T12:11:28Z |
| format | Article |
| id | doaj.art-5331f448a1fb496499633fc1f5b36efc |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-12-12T12:11:28Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-5331f448a1fb496499633fc1f5b36efc2022-12-22T00:24:52ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382022-06-0113212Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosisSeungwon RyuJae Woo ShinSoie KwonJiwon LeeYong Chul KimYoe-Sik BaeYong-Soo BaeDong Ki KimYon Su KimSeung Hee YangHye Young KimThe 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.https://doi.org/10.1172/JCI156876ImmunologyNephrology |
| spellingShingle | Seungwon Ryu Jae Woo Shin Soie Kwon Jiwon Lee Yong Chul Kim Yoe-Sik Bae Yong-Soo Bae Dong Ki Kim Yon Su Kim Seung Hee Yang Hye Young Kim Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis The Journal of Clinical Investigation Immunology Nephrology |
| title | Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis |
| title_full | Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis |
| title_fullStr | Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis |
| title_full_unstemmed | Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis |
| title_short | Siglec-F–expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis |
| title_sort | siglec f expressing neutrophils are essential for creating a profibrotic microenvironment in renal fibrosis |
| topic | Immunology Nephrology |
| url | https://doi.org/10.1172/JCI156876 |
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