Completed Cancer Infection & Immunity

Elucidating How Tissue Resident Regulatory T cells Contribute to Epithelial Stem Cell Homeostasis and Tissue Regeneration

Funder Wellcome Charity-funded
Recipient organisation King's College London
Funding £1.4M
Period Jan 2019 — Dec 2023

In plain English

AI plain-English summary

Regulatory T cells—immune cells that normally tamp down inflammation—are physically nestling into hair follicles in the skin, where they directly help stem cells regenerate tissue. This matters because the immune system’s role in controlling stem cells is largely unknown. The researchers have already shown that a specific subset of Tregs carries a signalling molecule called Jagged-1 on their surface, and that this molecule is essential for hair follicle stem cells to kick-start regeneration after injury. Without it, healing stalls. The problem is that no one knows how these Tregs acquire Jagged-1 in the first place, or whether the same mechanism operates in skin cancers. If the team succeeds, they will map the molecular wiring that turns a Treg into a stem-cell helper. This is fundamental science—there is no immediate clinical application. But because several new cancer and autoimmune therapies work by boosting or suppressing Tregs, understanding their normal tissue biology could eventually prevent unintended side effects, such as impaired wound healing or altered tumour growth, in patients receiving those treatments.

View original technical description
The maintenance of tissue homeostasis is dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T-cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of SCs (HFSCs). Recently, we have functionally dissected the role of Tregs in HFSC biology. Lineage-specific depletion revealed that Tregs promote HF regeneration by augmenting HFSC function. Transcriptional and phenotypic profiling of skin Tregs identified expression of the Notch ligand family member, Jagged-1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. To mechanistically dissect how Jag1 expression on Tregs is induced and how these cells represent a unique skin-resident population, we will initially perform comprehensive discovery approaches, at both the population and single cell level. We will also define the mechanistic contribution of Jag1+ Tregs in SC mediated regeneration in both healthy skin and skin tumors. Given that several new therapies for cancer and chronic inflammatory diseases are focused on augmenting the function of Tregs, it is imperative that we have a comprehensive understanding of the biology of Tregs in tissues.

View the original record at the funder ↗

Researchers

Niwa Ali (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Characterising the Tumour-Associated Regulatory T Cell Niche
Dissecting the code for regulatory T cell entry into the tissues and differentiation into tissue-resident cells
Novel approaches to determining the function of tissue-specific regulatory T cells
Genome organiser Satb1 and the control of tissue-specific chromatin remodelling during regeneration of the epidermis
The role of T cells in epithelial maintenance and regeneration.

Original classification

Sir Henry Dale Fellowship

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.