Date on Master's Thesis/Doctoral Dissertation
Microbiology and Immunology
Microbiology and Immunology, PhD
Committee Co-Chair (if applicable)
immunology; microbiota; IL-17; gamma delta; oral; gingivalis
IL-17 producing γδ T cells (γδT17) promote numerous autoimmune diseases such as psoriasis and arthritis, as well as, cancers of the colon, lung and breasts. Yet γδT17 peripheral regulation has yet to be thoroughly explored. In mice deficient in IL-17 signaling, we observed expansion of γδT17 in all major tissues. However, γδT17 expansion was not uniformly distributed systemically and was most prominent in oral draining cervical lymph nodes (LNs) with monoclonal expansion of Vγ6 γδT17. In vitro proliferation assays of these cervical LNs showed endogenous proliferation by γδT17 dependent on cell-to-cell contact with CD103+ DCs. CD86+ and CD80+ activated CD103+ DCs are increased in the oral draining LNs suggesting that perhaps microbiota-activated CD103+ DC expand γδT17. 16s rRNA FISH hybridization shows increase in 16s rRNA in oral draining LNs. Treatment of mice deficient in IL-17 signaling with α-LTBR-Ig (to remove LNs) or oral broad-spectrum antibiotics abrogates γδT17 expansion. Cohousing IL-17r-/- mice with wild type mice induces γδT17 expansion in the wild type mice also showing increase numbers of activated CD80+ and CD86+ CD103+ DCs in the oral draining LNs. In germ-free mice which lack microbiota, γδT17 expansion is significantly inhibited while γδT17 cells are expanded in a Porphyromonas gingivalis oral infection model. γδT17 are promoters of different devastating diseases and this study provides new evidence showing they can be regulated by CD103+ DCs providing a new and specific cell-to-cell interaction that could be targeted by future therapeutics.
Fleming, Christopher Jay, "Microbiota activated CD103+ DCS stemming from oral microbiota adaptation specifically drive γδT17 proliferation and activation." (2016). Electronic Theses and Dissertations. Paper 2445.