Abstract
Microbiota-driven regulatory T cells suppress experimental autoimmune encephalomyelitis (EAE) in interleukin-17A deficient HLA class-II transgenic mice model of multiple sclerosis (MS)
The Journal of immunology (1950), Vol.204(1_Supplement), pp.141-141.11
05/01/2020
DOI: 10.4049/jimmunol.204.Supp.141.11
Abstract
Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Despite IL-17A being linked to the immunopathogenesis of MS, the mechanism of IL-17A in disease development and maintenance is unclear. In the present study, we investigated the association of IL-17A and gut microbiota in disease development and severity, utilizing HLA-DR3 transgenic mice lacking IL-17A (IL-17A−/−). We found that HLA-DR3.IL-17A−/− mice had a higher frequency of CD4+CD25+FoxP3+ Treg cells and develop milder EAE compared to IL-17A suffcient HLA-DR3 mice. Utilizing 16S metagenocmic sequencing and analysis of gut microbiota we observed that HLA-DR3.IL-17A−/− mice had an increased abundance of regulatory T cells promoting bacteria in the gut such as Lactobacillus and Clostridia. Fecal transplantation followed by co-housing of HLA.DR3 mice with HLA-DR3.IL17A−/− resulted in development of milder EAE and an increase in CD4+CD25+FoxP3+ Treg cells in HLA-DR3 mice. Further whole-genome shotgun metagenomic analysis showed modulation of pathogen-associated molecular patterns (PAMPs) and O-antigen pathways linked with the host innate immune responses in HLA-DR3.IL-17A−/− mice. Thus our study suggests that gut microbiota changes due to the absence of IL17A induce regulatory T cells and suppresses disease in an animal model of MS by modulating the host-bacterial dynamics via PRR-PAMPS interactions.
Details
- Title: Subtitle
- Microbiota-driven regulatory T cells suppress experimental autoimmune encephalomyelitis (EAE) in interleukin-17A deficient HLA class-II transgenic mice model of multiple sclerosis (MS)
- Creators
- Shailesh K Shahi - University of IowaSamantha N Freedman - University of IowaAlexandra C Murra - University of IowaNicole Cady - University of IowaArnav Gupta - University of IowaNatalya V Guseva - University of IowaKatherine N Gibson-Corley - University of IowaAaron D Bossler - University of IowaSukirth M Ganesan - University of IowaNitin J Karandikar - University of IowaAshutosh K Mangalam - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.204(1_Supplement), pp.141-141.11
- DOI
- 10.4049/jimmunol.204.Supp.141.11
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2020
- Academic Unit
- Pathology; Periodontics; The University of Iowa Institute for Vision Research; Family Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984367713902771
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