T helper 17 cell

So cells have a lifespan, as we were talking about in earlier lectures.

So now you see acid sphingomyelinase generating ceramide controlling cell death, that is this particular type, apoptosis, can also be used via titrating its activity to control terminal differentiation, re-differentiation of cells like Tregs and Th17, inflammation associated with the immune cells and their response, and indeed senescence.

So senescence, remember, where the cell no longer divides at all.

So again, we talked about the neutral sphingomyelitis, now we're at the acidic.

When it comes to chronic hand eczema, certainly the atopic dermatitis component has this strong Th2 immune signal.

But when it comes to irritant contact dermatitis, for example, it has more of a Th1 or Th17 immune polarization.

And then when it comes to other types of chronic hand eczema, like allergic contact dermatitis, it's even more nuanced because it depends on the allergen.

So, for example, something like a metal, like nickel, may be more of a Th1, Th17 driver, but something like poison ivy might be more of a Th2 or Th22 driver.

And this is, again, speaks to what I said in the earlier question, that there is a heterogeneity and not only in the clinical morphology, but in the immune drivers of that morphology.

And this is why treating chronic hand eczema has historically been rather challenging because there are these different immune drivers, depending on what type or types of chronic hand eczema a patient has.

So then they saw that when it's knocked out, TBET went up as the next step.

And this TBET then led to, through a series of studies, much more active, you know, T cells, particular TH17 cells, which are known to be pathogenic in colitis models, right? And so you have this coding RNA.

When it goes away, TBET goes up, and that leads to pathogenic T cells.

And it's down, and it's FOXP3, makes you have more of this, you know, is kind of the hint of what's going on here, right? So...

And so what I'd like to do next is discuss the different mushrooms that I mentioned in the article, my 2022 article.

And the reason why I focused on those specific mushrooms is because some of them are well-known, like lion's mane, but then others, like reishi and cordyceps, And not just reishi and cordyceps, especially cordyceps as far as the effects that it has on the immune system, that Treg, Th17 balance.

Yeah, there's others that I'm not going to discuss here, but let's start with reishi.

So reishi, probably the most extensively studied medicinal mushroom.

So good source of polysaccharides is pretty much all mushrooms are.

Antioxidant activity.

Again, there are a couple of studies showing that it could potentially regulate Treg, Th17 balance, which is great.

Supports the gut microbiota.

talking about produce type 2 cytokines, including initially IL-5 and 13, but also IL-4, and sometimes people throw an IL-9 there, but that might be its own subset.

IL-C3s produce IL-17 as the quintessential cytokine from that population, and they're akin to Th17 cells.

So no one, as far as I know, have called them ILC17s, but just to make everything more confusing, we have to have these different numbers.

And ILC1s are also grouped with natural killer cells as well, because they are innate lymphoid cells that produce high levels of interferon gamma.

And interestingly, not surprisingly, these alarmans don't only have type 2 effects.

And so this is in part why...

there is some efficacy for tezopelomab in non-type 2 asthma as well, because there can be sort of this pro-neutrophilic or IL-C3, Th17 side that these alarmins can also promote.

And so we know our patients are complex, and there's a lot of mixed granulocytic, mixed endotype disease, And so the 33 story is tough because there can be homeostatic roles for 33.