My impressions of this discovery:
1) It actually proves that hair growth and cycling of terminal follicles is even MORE complicated than we thought. This may not be such a great thing, in terms of efforts to regenerate miniaturized hair follicles to cure baldness. Why? Because it adds a new wrinkle, and it's a BIG one. This probably explains why Aderans, Intercytex, Gho, etc. have failed in getting reliable and consistent growth and being able to develop a marketable cell-based hair regeneration treatment. It seems that a whole population of essential cells was being ignored because they had no idea these cells were needed to induce proper terminal growth. It's not like these cells are optional. Rather, this discovery indicates they're essential. So, to the extent that we don't have these Tregs cells near our follicles at the proper time, even injecting inductive DP cells or stem cells is not going to help much. It may help a little, but it's not guaranteed to rejuvenate these follicles.
2) From the diagrams and descriptions of the work, the Tregs are NOT part of the follicle, but rather, reside adjacent to the follicle, surrounding it, and send chemical signals to the HF stem cells to keep them activated. This is the first time we've seen a population of cells that is NOT native to the follicle, but which is required for the follicle to work properly. However, it raises a question: How to hair transplants work, then? Presumably the Tregs would be negatively affected by circulating DHT (they are somehow genetically DHT sensitive). But in hair transplants, healthy follicles from the back are moved to MPB affected areas. Tregs cells surrounding the follicle are NOT moved. If the Tregs cells in balding areas are missing then could transplanted donor follicles induce new Tregs cells to surround them? A lot of very complicated questions are raised here. Obviously, HT works, so somehow transplanted follicles must have the proper amount of working Tregs cells surrounding them.
3) If this is true, and Tregs cells are needed to make terminal follicles work in humans, it probably means that efforts like Dr. Kemp's, to rejuvenate or regenerate miniature MPB follicles will be even more difficult than anyone, even he, predicted. Ideally then, if he wants a viable cell injection based treatment, he'd have to replace not only DP cells, but also Tregs cells. But this is complicated by the fact that the injected Tregs cells probably will not stay in the area for more than 1 generation. Why would they? In vivo, there are probably some kind of Tregs progenitor cells, cycling to continuously produce new Tregs cells in the area. So, just injecting Tregs cells would probably not reestablish this regenerative cycle of creating new Tregs cells on a regular basis. I may be wrong about this, but I suspect this MIGHT be true.
4) What is it about the MPB phenotype, and DHT sensitivity, that depletes or eliminates the Tregs cells in balding areas? Is it something to do with increased PGD2? I have a hunch that PGD2 does have something to do with this. Maybe as PGD2 increases, the numbers of Tregs cells surrounding follicles decreases. (Tregs cells then go on to activate HF stem cells, but if there are no Tregs cells present, the HF stem cells aren't activated. The activated HF stem cells then migrate to the DP and induce more DP cells to proliferate. The DP cells proliferate a lot, secrete proteins, and cause a hair to grow.)
5) Question: Dr. Cotsarelis found that in balding areas, HF stem cells are still present in normal numbers, but they are not activated. They are dormant. How about Tregs cells? My understanding from the study is that they are not just hanging around in an inactive state; they are actually gone. Is this true?
Maybe @PKemp or @James_Bond have some ideas about this?