Interleukin 21

I mean, it seems that at the third stage you're seeing the T effector memory go up, the T reg go up, um, and then a TH17 go up, and then it drops off this cliff.

And I think, like the exhaustion markers that they point out, CTLA-4 and LAG-3, they really just rise, and then you see a real intensity, particularly of IL-21, of LAG-3, STAT4 in that L4 level.

So sort of the, you know, we talked about the little bit of a contraction, but also this, um, maybe there's a sort of parallel to what I tried to bring up with the B cells, with almost this exhausted regulatory-

Mm

They don't activate STAT3.

But if we give them IL-21, they do activate STAT3.

We, and the we here is Lauren Collin, who's a junior faculty also here at Children's, and she and Jody Wahed run our very early onset IBD clinic.

Together, we identified about seven patients that not only do they not activate when you give them IL-10, it doesn't work.

But when you give them the control hormone, IL-21, it didn't work either.

And so this was like, whoa, what are these patients? And what was unbelievably remarkable is that our first patient that I saw and was from a family from Georgia a number of years now was in the hospital for months, okay? And Tridon infliximab didn't work.

Tridon another agent didn't work.

We know what the T cell is doing.

It's making things called cytokines, interferon gamma, IL-21, and a very important one called IL-15, which I will come back to, and that's becoming a really interesting target.

So we know a lot about what the T cell is doing here to drive this process.

[musical interlude] The question, of course, is now for other autoimmune diseases, is there some dietary trigger? And then you react to your own proteins somehow.