Abstract
IL-17A control CNS inflammatory disease by regulating Treg cells through modulation of gut microbiota in HLA class-II transgenic mice model of multiple sclerosis (MS)
The Journal of immunology (1950), Vol.202(1_Supplement), pp.178-178.14
05/01/2019
DOI: 10.4049/jimmunol.202.Supp.178.14
Abstract
Abstract
Despite extensive studies on IL-17A in MS and its animal model EAE, the role of IL-17 in disease development and maintenance is unclear. We have previously established proteolipid protein-(PLP)91–110 induce EAE model in HLA-DR3 transgenic mice. In the present study, we investigated the role of IL-17A in disease development and severity utilizing HLA-DR3 transgenic mice lacking IL-17A (IL-17A−/−). We observed that HLA-DR3.IL17A−/− mice develop milder EAE than HLA-DR3 mice suggesting that IL17 is redundant for the development of EAE but might be required for the disease severity. Milder disease in HLA-DR3.IL17A−/− mice were due to an increase in CD4+CD25+FoxP3+ Treg frequency and suppressive function of Treg cells. Depletion of Tregs using anti-CD25 neutralizing antibody abrogated milder disease phenotype in HLA-DR3.IL17A−/− mice. As gut microbiota play an important role in the generation of Treg cells, we asked whether an absence of IL17A altered gut microbiota towards Treg promoting bacteria. Our 16s rRNA analysis of gut microbiota confirmed that IL-17 deficient mice had distinct gut microbiota than IL-17 sufficient mice with an increased abundance of Treg promoting bacteria such as Lactobacillus and Clostridia. Fecal transplantation studies are underway to confirm the role of Treg promoting gut bacteria. We next investigated whether IL-17F and GM-CSF can compensate for the absence of IL-17A. Interestingly blockage of both IL-17F and GM-CSF led to increased disease severity suggesting a protective role for IL-17F and GM-CSF. Thus our study suggests that there is a bidirectional link between the gut microbiota and IL-17A and the inverse relationship between IL-17A and Tregs might determine the susceptibility vs protection from EAE.
Details
- Title: Subtitle
- IL-17A control CNS inflammatory disease by regulating Treg cells through modulation of gut microbiota in 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 IowaKasra Zarei - University of IowaNatalya V Guseva - University of IowaKatherine Gibson-Corley - University of Iowa, The University of Iowa Institute for Vision ResearchAaron Bossler - University of IowaNitin J Karandikar - University of IowaAshutosh K Mangalam - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.202(1_Supplement), pp.178-178.14
- DOI
- 10.4049/jimmunol.202.Supp.178.14
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2019
- Academic Unit
- Pathology; The University of Iowa Institute for Vision Research; Family Medicine; Iowa Neuroscience Institute
- Record Identifier
- 9984654644402771
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