Defining the development and function of Tmic cells

Our lab is interested in unconventional and innate-like cells (such as MAIT cells) and what their role is in immune protection and pathology.Tmic cells are one such cell - a recently described subset of T helper cells which are Microbially reactive, Innnate-like and Class II restricted. These cells are abundant in the human colon and marked out by high expression of CD161 – a feature normally associated with unconventional T cells – along with other evolving markers. However, as well as behaving like innate-like cells they bear conventional TCRs and are restricted by MHC Class II. They are also found in mice where they adopt a double negative phenotype over time in response to gut commensals. We think these cells are important in gut homeostasis (also other organs potentially) and we have shown they are involved in inflammation, but there are many questions as to their origin and overall functionality to be answered.

This project would explore the development of these cells using CBIR mice which over-express a commensal-reactive TCR, first by scRNASeq and scATACseq to define the steps along the pathway from conventional tissue memory to Tmic phenotype. Secondly using spatial transcriptomic methods to define their colocalization in the steady state and after challenge. Finally we will use a new in vivo CRISPR screen method (CHIME) to define the critical steps in development of Tmics and explore their functions in vivo. We will aim to compare mouse and human Tmic populations to define this novel conserved cell population and explore its role in health and disease.

Reference: https://www.nature.com/articles/s41467-022-35126-3