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Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells
- Source :
- European journal of immunology. 48(12)
- Publication Year :
- 2018
-
Abstract
- Primary sclerosing cholangitis (PSC) is a severe chronic liver disease of the small and large bile ducts. The pathogenesis is unknown but a strong immune cell component has been suggested. Mucosal-associated invariant T (MAIT) cells are abundant in human liver and localize around bile ducts. Yet, the role of MAIT cells in PSC remains unclear. Here, we performed a detailed characterization of MAIT cells in circulation and assessed their presence in bile ducts of PSC patients as well as non-PSC controls. We observed a dramatic reduction in MAIT cell levels in PSC patients. High-dimensional phenotypical analysis using stochastic neighbor embedding revealed the MAIT cells to be activated, a phenotype shared by the investigated disease control groups. In line with the noted phenotypic alterations, MAIT cell function was reduced in response to Escherichia coli and to cytokine stimulation in PSC patients as compared to healthy controls. Using a novel sampling approach of human bile ducts, we found MAIT cells to be specifically enriched within bile ducts. Finally, distinct from the dramatic decline observed in circulation, PSC-patients had retained levels of MAIT cells within bile ducts. Altogether, our results provide a detailed insight into how the human MAIT cell compartment is affected in PSC.
- Subjects :
- 0301 basic medicine
Adult
Male
Pathology
medicine.medical_specialty
Immunology
Cell
Cholangitis, Sclerosing
Inflammation
Mucosal associated invariant T cell
Biology
Chronic liver disease
digestive system
Inflammatory bowel disease
Mucosal-Associated Invariant T Cells
Primary sclerosing cholangitis
Immunophenotyping
Pathogenesis
03 medical and health sciences
Immune system
medicine
Escherichia coli
Immunology and Allergy
Humans
Cells, Cultured
Escherichia coli Infections
Aged
digestive, oral, and skin physiology
Middle Aged
medicine.disease
digestive system diseases
030104 developmental biology
medicine.anatomical_structure
Blood Circulation
Cytokines
Female
Bile Ducts
medicine.symptom
Subjects
Details
- ISSN :
- 15214141
- Volume :
- 48
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- European journal of immunology
- Accession number :
- edsair.doi.dedup.....db6a5413abee8266db04cd8d122ea18c