FOXP3

In particular, calcitriol lowers interleukin 22, an inflammatory marker, induces regulatory T cell differentiation, which you need to help fight infections.

Vitamin D promotes the development of Treg cells that express CTLA and Fox P3, which are immune supportive cells.

Vitamin D and its receptor have potential pain signaling capabilities by inducing the expression of nerve growth factor.

Well, what do you have damage of in Guillain-Barré syndrome? Nerves.

And among all the immune cells, T cells, of course, are absolutely necessary for controlling tumor progression.

So if you go look at melanoma, melanoma patients, in fact, not the murine model, the ratio of cytotoxic CD8 positive T cells versus CD4 positive, FOXP3 positive Tregs in the tumor microenvironment is predictive to the disease outcome.

Because the infiltration of Tregs into the tumor is the critical step that promotes tumorigenesis because the Tregs are shutting down the T effector cell activity.

So, neuropylon 1, which is highly expressed in Tregs, it's a protein, regulates the migration of Tregs into a VEGF-producing tumor tissue, and that's accompanied by direct elevation of tumor progression.

So they then did some studies trying to figure out what regulates it.

And establish that it's regulated by the RNA exosome, FOXP3, and C-rel are things that can make this go up and down.

Okay.

We're mostly up, right? Like, so this turns them up.

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...

Then they try to figure out how it was recruited.

And not only on those DCs, on other innate immune cells.

And what that does when niacin binds to that G-protein coupled receptor in these cells is it's going to induce FOXP3 expression.

in naive T cells.

It's correct.

Now, here's where vitamin D rolls in.

Vitamin D3, through its metabolite, as I mentioned, 125-didroxyd3, working through the vitamin D receptor VDR, further capitulates Tregs because it enhances FOXP3 gene transcription.

by binding to the FOXP3 promoter locus.

That would be the promoter enhancer regions.

What are these markers? Because most of our audience are pathologists, so...

Yeah, so we have CD4 for T helper cells and FOXB3.

So in combination with CD4, we can see Tregs.

We have CD8 for cytotoxic T cells, CD68 for macrophage and CD20 for B cells.

I have a message from listener Cecilia, who wrote, "March is Autoimmune and Endometriosis Awareness Month.

It's interesting to see the new research coming out, such as new blood tests for endo and the Nobel Prize for, uh, the FOXP3 gene." So first off, uh, Cecilia mentioned the Nobel Prize for FOXP3.

Uh, this is a protein that plays a huge role in autoimmune disease because one of its job is to control regulatory T cells.

I feel like it's a very, like, who watches the watchmen kind of situation.

So you can put a lot of the mutine, and it's not gonna activate, uh, T cells that don't express this receptor.

Um, but what they find is that although it works really nice in vitro, once you put the cells in mice and you inject the, the cytokine in the mice, it doesn't seem to help increase amount, number of Tregs or the, the expression of CD25 and FoxP3, which kind of a indicator of, of proper stimulation.

Um, so they don't protect of the mice, uh, for i-in a, um, diabetes type 1, uh, mouse model.

So although they work in vitro, in vivo, it doesn't seem to, to, to be sufficient.