Andrew J. Bryant

Parsing the STING in pulmonary hypertension— @ajbryantlab & team @UF report on opposing roles for STING in PH—a paradigm shifting mechanism suggesting we refocus on treatments that target cell-specific inflammatory activation: insight.jci.org/articles/view/…

The findings you highlight from the @ajbryantlab team about STING's varying roles are truly fascinating! They propose a crucial shift in how we approach inflammation-driven diseases like pulmonary hypertension. Focusing on the cell-specific activity could lead to more effective treatments. How might these insights change current therapeutic strategies? It's incredible to see science challenging our understanding of such complex mechanisms. For further exploration of biomedical questions, check out sciqst.com, your go-to platform for generating comprehensive biomedical reviews. #Medicine #PulmonaryHypertension

STING and PH? Check it out!

"Opposing roles for myeloid and smooth muscle cell STING in pulmonary hypertension" by @ajbryantlab & team insight.jci.org/articles/view/…

Ever wonder how smooth muscle and inflammatory cells act through a common mediator in causing pulmonary hypertension? STING may be the answer. JCI Insight - Opposing roles for myeloid and smooth muscle cell STING in pulmonary hypertension #top" target="_blank" rel="nofollow noopener">insight.jci.org/articles/view/…

The common TMEM173 HAQ, AQ alleles rescue CD4 T cellpenia, restore T-regs, and prevent SAVI (N153S) inflammatory disease in mice; great work from our collaborator Lei Jin! elifesciences.org/reviewed-prepr…

SEE YOU NEXT TIME!!

@atvbahajournals Based on our studies, no, cell-to-cell contact is not necessary, as it appears to be a paracrine or even autocrine effect. Uncertain about the mechanism, as of now, but appears to be intimately related to HIF-signaling. @joeydai thoughts?

0⃣9⃣ @ajbryantlab The effect of STING KO on VEGF production from monocytes is interesting, how? Do monocytes need to be in contact with ECs?

@atvbahajournals We are still exploring this, so forgive the “hand-waving” when I simply say regulation of cellular senescence pathway in innate immune cells. When we knock STING out of myeloid cells, it makes PD-L1 expression go up, for what that’s worth.

0⃣8⃣ @ajbryantlab How do you think STING affects PDL-1 expression in hypoxia-induced PH?

@MaAlfaidi @ArcSuellen @HaoYin20 @joeydai @atvbahajournals PMID 33738095

@ajbryantlab @ArcSuellen @HaoYin20 @joeydai @atvbahajournals Thank you very much, how fascinating that is, could you share the PMID here! I would love to read more!!!

I can echo Andrew, we also did not observe exaggerated PH phenotype when sting is co-deleted with Egln1 in EC.

@MaAlfaidi @ArcSuellen @HaoYin20 @joeydai @atvbahajournals Mitochondrial and nuclear DNA have been implicated. We haven’t looked upstream much, just because the data on DNA damage is so robust. We write a review in Pulmonary Circulation on the topic, if you wanted a more thorough answer.

@ArcSuellen @HaoYin20 @joeydai @atvbahajournals Thank you very much @HaoYin20 Can you share PMID? I am interested in reading on how STING is linked to MMPs/TIMP in SMC? what do you mean for "cytosolic DNA"? Mitochondrial? How? @ajbryantlab any speculations or have you observed any of that in your studies? Thanks

@MaAlfaidi @atvbahajournals @Kanika0386 Oh… several, but really only 4-5 main variants. None are linked to PH, but we are hopefully going to report on this in the upcoming months with our collaborator Lei Jin.

@ajbryantlab @atvbahajournals @Kanika0386 How many variants are there in human? also, are there any mutations linked to PAH? Thank you!

0⃣5⃣ @ajbryantlab What are the next research steps to understand STING's role in preventing right-heart failure in end-stage PH, and how might this inform new therapies? @Kanika0386

@dlljj @atvbahajournals Agreed, and can’t wait to read your report. What was your model? Or I can just wait to read it. Congrats!

@ajbryantlab @atvbahajournals Our paper should be out soon in Red journal. We just did global KO and H-151 treatment. Quite interesting why EC-specific KO have no phenotype.

0⃣4⃣ @ajbryantlab Your finding of the high STING expression in the muscular arteries in patients with pulmonary hypertension is interesting, what the primary cells?

@MaAlfaidi @atvbahajournals Absolutely, that could make a difference. Cell-to-cell communication is key. DNA is fundamentally supposed to be kept inside, right. If you saw a friend covered in blood (an inside fluid) it would alert you differently to potential danger versus if they simply waved hello.

@ajbryantlab @atvbahajournals Thank you very much for sharing. That is an interesting observation, do you think beside the expression, might be differences in the signaling, especially in vascular cells vs. immune cells? Also, might be altered with the course of treatment?

0⃣6⃣ @ajbryantlab Can you please expand on your animal model and why you chose that? Which stage of the disease it is mimicking?

@atvbahajournals @Kanika0386 I personally believe part of the answer lies in the functional allelic variance of STING across a broad patient population. We are looking in to this in a cursory fashion - more data to present soon!

@atvbahajournals @Kanika0386 Fantastic point, and thank you. Truth is, we are not quite sure. Foreign and self-DNA recognition lie at the heart of these disorders, so almost certainly similar mechanisms, but cell and tissue tropism is odd for such an ubiquitous cellular response.

0⃣7⃣ @ajbryantlab How does STING's function in PH compare to its roles in lung fibrosis, cancer, and autoimmune conditions? @Kanika0386