Regulatory T cells are a part of the adaptive immune system and the key to putting brakes on unwarranted responses by overactive T cells and B cells. Because of this ability, regulatory T cells (T-reg cells) have a central role in maintaining tissue homeostasis and self-tolerance, the ability of the immune system to recognize self-made antigens as non-threatening.
What's new, various studies have discovered a different role for T-reg cells. Not only do they suppress the immune system from attacking a given individual's tissues (autoimmune disease), but the cells can help make hair grow.
It was long thought of that hair stem cells worked independently in regeneration, yet it has now been shown that T-reg cells stimulate hair stem cells, functioning in tissue repair. If the T-reg cells are removed when follicle regeneration normally occurs, hair ceases to grow back.
Through a system of cell-cell communication known as the Notch pathway, T-reg cells can trigger hair follicle generation. This pathway is highly conserved across evolution and widespread in its functions; broken down, the pathway can serve in cell proliferation, differentiation, and apoptosis (programmed cell death). It is especially involved in the development of sensory hair cells.
In mammals, there are two main types of ligand (binding site) families involved in the pathway - the jagged protein family, which includes JAG1 and JAG2, and the delta-like protein family, which includes DLL1, DLL3, and DLL4. Binding to the ligand are the receptors, of which there are four types in mammals. Currently, the applications for notch receptors are being heavily researched in fields of cancer and in synchrony with research on CAR T cells.
Expression of the ligand JAG1 is largely important in how the Notch pathway functions. On a rudimentary level, the correct molecular structure of a ligand is necessary for a receptor to bind and a response to be triggered. Thus, the lock-and-key fit of JAG1 to a notch receptor is a crucial component in cell-cell communication.
Removing the JAG1 protein results in a disruption of the pathway; the notch receptor is not able to bind to the protein, so the sending cell (T-reg cell) cannot induce an intracellular response in the receiving cell (hair stem cell), which would normally include making transcription factors that aid in the activation of genes involved in stem cell proliferation.
Glucocorticoid signaling, a different type of ligand-based signaling that involves the induction of transcription factors involved in stem cell proliferation, has also been shown to be a vital ingredient to activating stem cells from T-reg cells. Similar results amounted from studies that sought to see whether removal of glucocorticoids had any effect on the instruction of T-reg cells.
Many genes associated with alopecia have been found to correlate with T-reg cell deficiencies. Therefore, it is necessary to understand the relationship between T-reg cells and hair stem cells to uncover more about how alopecia comes about as an autoimmune disease.
Sources
Anjali A. Sarkar, P. (2023, June 5).
Hair regeneration requires regulatory T cells signal skin stem cells. GEN. https://www.genengnews.com/news/hair-regeneration-requires-regulatory-t-cells-signal-skin-stem-cells/
JJ Medicine. (2017, December 29).
Notch signaling pathway | purpose and mechanism. YouTube. https://www.youtube.com/watch?v=Pm35bSqlh6c
Wang, X., Liu, Y., He, J., Wang, J., Chen, X., & Yang, R. (2022, July 4).
Regulation of signaling pathways in hair follicle stem cells. Burns & trauma. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250793/
Weiler, N. (2017).
New hair growth mechanism discovered. New Hair Growth Mechanism Discovered | UC San Francisco. https://www.ucsf.edu/news/2017/05/407121/new-hair-growth-mechanism-discovered
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