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Short-chain fatty acid butyrate induces IL-10-producing B cells by regulating circadian-clock-related genes to ameliorate Sjögren's syndrome
- Source :
- Journal of autoimmunity. 119
- Publication Year :
- 2020
-
Abstract
- Objectives Sjogren's syndrome (SS) is an autoimmune disease caused by inflammation of the exocrine gland. The pathological hallmark of SS is the infiltration of lymphocytes into the salivary glands. Increased infiltration of T and B cells into salivary glands exacerbates symptoms of SS. Several recent studies have identified the role of gut microbiota in SS. Butyrate, one of the metabolites of the gut microbiota, regulates T cells; however, its effects on B cells and SS remain unknown. This study determined the therapeutic effect of butyrate on regulating B cells in SS. Methods Various concentrations of butyrate were intraperitoneally injected three times per week in NOD/ShiLtJ (NOD) mice, the prototype animal model for SS, and observed for more than 10 weeks. Whole salivary flow rate and the histopathology of salivary glands were investigated. Human submandibular gland (HSG) cells and B cells in mouse spleen were used to confirm the anti-inflammatory and immunomodulatory effects of butyrate. Results Butyrate increased salivary flow rate in NOD mice and reduced inflammation of salivary gland tissues. It also regulated cell death and the expression of circadian-clock-related genes in HSG cells. Butyrate induced B cell regulation by increasing IL-10-producing B (B10) cells and decreasing IL-17-producing B cells, through the circadian clock genes RAR-related orphan receptor alpha and nuclear receptor subfamily 1 group D member 1. Conclusion The findings of this study imply that butyrate may ameliorate SS via reciprocal regulation of IL-10- and IL-17-producing B cells.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Exocrine gland
Immunology
Butyrate
Models, Biological
Salivary Glands
Immunophenotyping
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Mice, Inbred NOD
Internal medicine
Circadian Clocks
medicine
Immunology and Allergy
Animals
B cell
NOD mice
030203 arthritis & rheumatology
Mice, Knockout
B-Lymphocytes
Salivary gland
Stem Cells
Interleukin-17
Sodium butyrate
Cell Differentiation
Nuclear Receptor Subfamily 1, Group F, Member 1
Submandibular gland
Immunohistochemistry
Interleukin-10
Interleukin 10
Butyrates
Disease Models, Animal
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Basic-Leucine Zipper Transcription Factors
Sjogren's Syndrome
chemistry
Gene Expression Regulation
Nuclear Receptor Subfamily 1, Group D, Member 1
Disease Susceptibility
Biomarkers
Subjects
Details
- ISSN :
- 10959157
- Volume :
- 119
- Database :
- OpenAIRE
- Journal :
- Journal of autoimmunity
- Accession number :
- edsair.doi.dedup.....075aefc4addb5df23536426c9f387605