Interleukin-17A

What they found was that in HS lesions, right, you have all these inflammatory cytokines that are extremely increased.

You know, things like IL-17A, F, uh, TNF-alpha.

You have interferon gamma.

You have interleukin, uh, IL-1 beta in there, which is really, uh, highly control... or highly kind of associated with neutrophil chemotaxis.

And what they found was that that is also just a huge, giant mass of different inflammatory cells.

And so you have that, and you have the tunnels, and that's causing a lot of inflammation as well.

And what we're seeing is this extreme increase in the different inflammatory cytokines that I was talking about earlier, things like IL-17A and F.

And what's interesting is I always get asked the question about, like, why does F matter so much, e- especially in HS? And it's because we found that when you do, like, these different biopsies, that there are cells, uh, that are only expressing IL-17F.

Oh, sorry.

So TH17, IL-17A, and IL-17F.

So those three are associated.

These cytokines act directly on the keratinocytes, prompting them to release other chemokines like CXCL1 and CXCL8.

Dendritic cells secrete IL-23.

That IL-23 is what's required for the survival, expansion, and maintenance of the Th17 cells.

So then those Th17 cells that are surviving because of IL-23 produce IL-17A, IL-17F, and IL-22.

Those cytokines are directly responsible for driving the keratinocyte hyperproliferation.

It binds to the IL-23 receptor on responsive immune cells.

That contributes to downstream signaling and the release of inflammatory mediators, including IL-17A, IL-17F, IL-19, and IL-22.

Those signals can drive abnormal activation and proliferation of keratinocytes, the major cells in the outer layer of the skin.

The visible result is thickened, inflamed, scaly plaque associated with psoriasis.

We need to teach more on this.

An open-label study of calcinosis cutis in juvenile dermatomyositis patients.

You know, we see calcinosis in our scleroderma patients.

We see it occasionally in dermatomyositis.

It's a bigger problem in JDM in the pediatric population.

And this study of open-label study of 20...

JDM patients, 11 boys, age 10.

They had calcinosis cutis for 31 months.

The first article, entitled Asthma in Older Adults, Clinical Patterns, Inflammatory Phenotypes, and Practical Management, explains that asthma in older adults is shaped by immunosenescence and inflammaging, which shift airway disease toward neutrophilic or mixed, often T2 low inflammation, and may help explain reduced responsiveness to inhaled corticosteroids.

It contrasts older adults with younger patients, noting that older patients more often show higher neutrophils and inflammatory mediators such as IL-6, IL-8, IL-1 beta, and IL-17A, though eosinophilic phenotypes still occur in some late-onset or severe cases.

Clinically, it supports practical management strategies such as leukotriene receptor antagonists as add-on or steroid-sparing therapy and summarizes evidence that biologics including omelizumab, mepolizumab, benrolizumab, reslazumab, depilumab, and tezopelumab can remain effective and reasonably safe in older adults with severe asthma.

The overall conclusion is that older adult asthma is biologically and therapeutically distinct enough that management should be phenotype aware, comorbidity aware, and designed to limit corticosteroid burden.

And I worry about that because we need to understand that it is complex.

Like, for example, my biggest thing about this is, you know, that one study that I was talking about earlier out of Jim Kruger's lab, what they found was that in HS lesions, right, you have all these inflammatory cytokines that are extremely increased, you know, things like IL-17A, F, TNF-alpha, you have interferon gamma, you have interleukin IL-1 beta in there, which is really highly kind of associated with neutrophil chemotaxis.

And so it's like, what does that do? And then what's crazy is what they found was that You have that in the HS lesion.

And then when you go to perilesional skin, so about two centimeters out from the end of the inflammatory lesion.