ILC2s are plastic & can switch b/w pro or anti-inflammatory forms. Inflammatory ILC2s are the major source of IL-17A in mouse ARDS model. In this paper, designated as pILC3s (c-kit+).
atsjournals.org/doi/full/10.11…
nature.com/articles/s4157…
Three papers demonstrating TGF-β polarizes ILC2s into IL-17A producing cells in presence of NLRP3 cytokines.
ILC2s+ TGF-β + IL-1β + IL23 -> IL-17A
ncbi.nlm.nih.gov/pmc/articles/P…
nature.com/articles/s4159… (31263279)
ncbi.nlm.nih.gov/pmc/articles/P…
Bringing this back to covid-19, people are looking for explanation for inflammation occuring in tissues outside lungs - skin, kidney, vessels, brain, heart, prostate. I've seen several reports now proposing virus is infecting these tissues. Outside context of sepsis, unlikely
So how could inflammation occur distal to the infection sites w/o virus entering blood or magically "jumping" into other tissues?
(Tbc, not suggesting viremia never occurs, but no evidence it explains kidney damage or skin manifestations, for eg).
onlinelibrary.wiley.com/doi/abs/10.111…
Here's hypothesis:
Distal inflammation is mediated by tissue resident immune cells in response to dysregulated cytokine response caused by SARS-CoV-2 (triggering of inflammasome & suppression of IFN responses).
Who wants to bet on this one? Feeling 🧠🔥😉