Gut and lung microbial dysbiosis associated with T cell mediated inflammation in Treg-deficient autoimmune mice

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B119
Abstract ID: 4092

Presenting Author:
Yuying Liu , Associate Professor at UT Hlth. Houston McGovern Med. Sch.

Abstract:

In the Foxp3⁺Treg deficient scurfy (SF) mouse, a mouse model of human IPEX syndrome, we showed dynamic changes of autoimmunity and gut microbial dysbiosis during the first 22 days of life.  Our aims in this study were to identify lung microbiota by 16S rRNA gene sequencing and to assess T cell mediated lung inflammation. We observed a tendency toward reduced Shannon diversity, with significantly shifted clusters between SF and WT assessed by principal coordinates analysis. Lung bacterial taxa had increased relative abundance (RA) of Bacteroides, Parabacteroides, and Others_uncategorized. SF Lungs had reduced RA of Lactobacillus and Ruminococcus bromii (all, p<0.05).  While both gut and lung show significant microbial dysbiosis, the SF lung histology demonstrated lymphocyte infiltration and proteinaceous debris that filled airspaces.  The areas of lymphocyte infiltration in lungs correlated with % of circulating inflammatory CD4⁺T cells. We found increased IL-1β in the lung tissue homogenates, with increased IL-2, IFN-γ and IL-4 in the SF plasma. When we adoptively transferred CD4⁺T cells isolated from the spleen of SF mice via intraperitoneal injection to Rag1KO mice, Rag1KO mice developed lung inflammation. In conclusion, Treg-deficiency causes CD4⁺T cell-driven inflammation, associated with microbial dysbiosis in lung and gut. Future studies may focus on investigating dysbiosis and modulating microbiota to treat Treg-deficiency-associated autoimmune diseases.