1/ thread on ARDS, innate lymphoid cells, & IL-17A
IL-17A stimulates production of other pro-inflammatory cytokines, including IL-6, IL-8, G-CSF, MCP-1, & TNF-a & promotes macrophage & neutrophil recruitment.
IL-17A stimulates production of other pro-inflammatory cytokines, including IL-6, IL-8, G-CSF, MCP-1, & TNF-a & promotes macrophage & neutrophil recruitment.
2/
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…
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…
3/ ILCs can be tissue resident (go to tissue during fetal development and stay) & are found in different places around the body like the gut, respiratory tract, skin, kidney, brain, & heart.
4/ ILCs contribute to both innate & adaptive immune responses and were only recently discovered. Nice review about them here.
nature.com/articles/s4157…
nature.com/articles/s4157…
5/
It's been shown that in some chronic inflammatory conditions, the population of ILCs is shifted. For eg, the lungs of people with COPD have more IL-17A producing ILCs. This likely contributes to COPD's neutrophilic inflammation.
It's been shown that in some chronic inflammatory conditions, the population of ILCs is shifted. For eg, the lungs of people with COPD have more IL-17A producing ILCs. This likely contributes to COPD's neutrophilic inflammation.
6/
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…
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…
7/
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
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
8/
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…
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…
9/
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 🧠🔥😉
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 🧠🔥😉
