Loss of Acid Ceramidase in Myeloid Cells Protects From Chronic Colitis in IL10-Deficient Mice.
9 affiliations
- 1Physiological Sciences GIDP, University of Arizona, Tucson, Arizona, USA.
- 2School of Nutritional Sciences and Wellness, University of Arizona, Tucson, Arizona, USA.
- 3University of Arizona College of Medicine, University of Arizona, Tucson, Arizona, USA.
- 4University of Arizona College of Science, University of Arizona, Tucson, Arizona, USA.
- 5Department of Pediatrics, Steele Children's Research Center, Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, University of Arizona Health Sciences Center, Tucson, Arizona, USA.
- 6University Animal Care, The University of Arizona, Tucson, Arizona, USA.
- 7University of Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA.
- 8Department of Immunobiology, University of Arizona, Tucson, Arizona, USA.
- 9BIO5 Institute, University of Arizona, Tucson, Arizona, USA.
Abstract
Patients with inflammatory bowel disease exhibit elevated expression of acid ceramidase (AC), an enzyme in sphingolipid metabolism. Recent studies have shown that myeloid cells contribute to the elevated expression of AC, such that the conditional loss in these cell types protects from acute colitis. We crossed conditional ASAH1 LyzMCRE knockout mice with IL10 knockout mice to determine the role of AC in a model of spontaneous, chronic colitis. Colon tissues were analyzed for lipids, mRNA, and protein. We performed flow cytometry to determine the role of myeloid AC in recruiting immune cells in disease. In this study, the conditional loss of AC in myeloid cells protected from chronic colitis, reduced markers of inflammation, increased ceramides in the colon, and reduced the inflammatory metabolite sphingosine-1-phosphate (S1P). Recruitment of immune cells into intestinal tissue was significantly impaired, specifically recruitment of neutrophils and effector Th1/Th17 T cells. The findings from this study indicate that AC may be a promising therapeutic target for patients with inflammatory bowel disease by modulating sphingolipid metabolism in immune cells.
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BibTeX
@article{espinoza2026loss,
title = {{Loss of Acid Ceramidase in Myeloid Cells Protects From Chronic Colitis in IL10-Deficient Mice.}},
author = {Keila S Espinoza and Brandon K Dahl and Ella M Ryan and Mary R Gordon and Chelsea L Doll and Marilyn T Marron and Cameron A Beard and Pujarini D Dey and David G Besselsen and Richard J Simpson and Justin M Snider and Justin E Wilson and Pawel R Kiela and Ashley J Snider},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
year = {2026},
month = oct,
doi = {10.1096/fj.202602342rrr},
url = {https://europepmc.org/article/MED/42886684},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Loss of Acid Ceramidase in Myeloid Cells Protects From Chronic Colitis in IL10-Deficient Mice.
AU - Keila S Espinoza
AU - Brandon K Dahl
AU - Ella M Ryan
AU - Mary R Gordon
AU - Chelsea L Doll
AU - Marilyn T Marron
AU - Cameron A Beard
AU - Pujarini D Dey
AU - David G Besselsen
AU - Richard J Simpson
AU - Justin M Snider
AU - Justin E Wilson
AU - Pawel R Kiela
AU - Ashley J Snider
PY - 2026
DA - 2026/10/01
JO - FASEB journal : official publication of the Federation of American Societies for Experimental Biology
DO - 10.1096/fj.202602342rrr
UR - https://europepmc.org/article/MED/42886684
AB - Patients with inflammatory bowel disease exhibit elevated expression of acid ceramidase (AC), an enzyme in sphingolipid metabolism. Recent studies have shown that myeloid cells contribute to the elevated expression of AC, such that the conditional loss in these cell types protects from acute colitis. We crossed conditional ASAH1 LyzMCRE knockout mice with IL10 knockout mice to determine the role of AC in a model of spontaneous, chronic colitis. Colon tissues were analyzed for lipids, mRNA, and protein. We performed flow cytometry to determine the role of myeloid AC in recruiting immune cells in disease. In this study, the conditional loss of AC in myeloid cells protected from chronic colitis, reduced markers of inflammation, increased ceramides in the colon, and reduced the inflammatory metabolite sphingosine-1-phosphate (S1P). Recruitment of immune cells into intestinal tissue was significantly impaired, specifically recruitment of neutrophils and effector Th1/Th17 T cells. The findings from this study indicate that AC may be a promising therapeutic target for patients with inflammatory bowel disease by modulating sphingolipid metabolism in immune cells.
SN - 0892-6638
SN - 1530-6860
ER -