Regulation of Tissue-Resident Memory T cell Development
Our work has shown that tissue-resident memory T cells (TRM) are phenotypically and functionally distinct to memory T cells in the circulation. We found that TRM development is a multistep process that requires the action of several molecules, and that TRM cells acquire a unique transcriptional profile during their differentiation (Figure 1). We are currently investigating regulatory cues that govern TRM cell development, with a focus on transcription factors that regulate commitment to the TRM cell lineage.
Figure 1: The developmental pathway of TRM cell formation.TRM precursors lacking KLRG1 enter the skin where they may (i) die in situ, (ii) return to the circulation or (iii) migrate to the epidermis. Note: Both tissue exit and epidermal entry are sensitive to treatment with pertussis toxin (PTx) indicating the involvement of chemokine receptors. Following epidermal entry, TRM precursors receive signals that instruct TRM differentiation and undergo maturation into long-lived CD103+ TRM cells in a TGF-β- and IL-15-dependent manner. Epithelial TRM cells and their counterparts in the circulation are depicted with different symbols to highlight their distinct transcriptional profiles.
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