Greg Hayes

#ToPrimeOrNotToPrime, this is the question! Excited for our new review @cp-trendsimmuno.bsky.social with @oceanedufies.bsky.social in which we discuss what is “priming” for the #NLRP3 #inflammasome & how we can harness this knowledge to better control human diseases! #InflammasomePower! #Free 👇👇👇

Human genetic errors of immunity illuminate an adaptive arsenal model of rapid defenses New discoveries in the field of human monogenic immune diseases highlight critical genes and pathways governing immune responses. Here, I describe how the ~500 currently defined human inborn errors of...

Human genetic errors of immunity illuminate an adaptive arsenal model of rapid defenses

www.cell.com/trends/immun...

Caspase-11 Mediated Hyperinflammation Impairs CD8⁺ T Cell Immunity and Viral Clearance in Severe SARS-CoV-2 Infection @biorxivpreprint.bsky.social
www.biorxiv.org/content/10.1...

Nirmatrelvir/ritonavir use reduces risk for long COVID in patients with immunodeficiency url: rupress.org/jhi/article/...

This paper strongly echoes the framework I have been developing and publicly advocating for over the last five years.

#MISC #KD #LongCovidKids

Multisystem inflammatory syndrome in children is a SARS-CoV-2 triggered Kawasaki disease - Pediatric Research Pediatric Research - Multisystem inflammatory syndrome in children is a SARS-CoV-2 triggered Kawasaki disease

Multisystem inflammatory syndrome in children is a SARS-CoV-2 triggered Kawasaki disease

www.nature.com/articles/s41...

Gut microbiota alterations are linked to COVID-19 severity in North African and European populations - npj Biofilms and Microbiomes npj Biofilms and Microbiomes - Gut microbiota alterations are linked to COVID-19 severity in North African and European populations

Gut microbiota alterations are linked to COVID-19 severity in North African and European populations

www.nature.com/articles/s41...

NLRP3 as a protein thermosensor !

By understanding the overlap between inflammatory diseases with shared genetic modulators, we can better ascertain the implications for other diseases with similar phenotypes.”

We propose that gut immunity may also be important in the development of KD, although further work is needed to elucidate this link.

Unravelling γδ T-cell dysregulation in the gut and its implications for immune-mediated diseases Summary: Gut immunity may play a critical role in the initiation and persistence of multisystem inflammatory syndrome in children, inflammatory bowel disease and Kawasaki disease. Understanding this c...

Common mechanisms across MIS-C, KD & IBD → the gut as a central driver

Great perspective from @sanchoshimizu.bsky.social — Unravelling γδ T-cell dysregulation in the gut and its implications for immune-mediated diseases

journals.biologists.com/dmm/article/...

Notably, WTA is not a PAMP.
Rather, WTA controls the release of bacterial DNA into cells, where it can act as a PAMP for AIM2 and cGAS. How many other meta-PAMPs are out there?
@jordanjastrab.bsky.social @harvardmed.bsky.social @bostonchildrens.bsky.social @harvardmicro.bsky.social

bsky.app/profile/soun...

An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon | Journal of Virology Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an ongoing public health challenge as a cause of acute illness and post-acute sequelae of COVID-19 (PASC, or long COVID). Our stud...

An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon | Journal of Virology

From spike to suppression: the RGD motif fuels TGF-β and disables antiviral immunity

#PASC #LONGCOVID

journals.asm.org/doi/10.1128/...

How interactions between oxidized DNA and the NLRP3 inflammasome fuel inflammatory disease | Review

www.sciencedirect.com/science/arti...

Moving forward it’s critical to learn from the little we do know about Systemic Auto Inflammatory Diseases (SAID) which has only started to be defined and recognized since Dan Kastner and colleagues at the NIH first coined the term in 1999.

Auto-inflammation isn’t confined to rare syndromes. It can also be innate immune hypersensitivity / dysfunction expressed across a spectrum — from monogenic diseases like CAPS, through post-infectious syndromes like MIS-C and KD, to chronic conditions like ME/CFS and Long Covid.

Overactive Immune System Seen in Patients with Chronic Fatigue Syndrome (ME/CFS) Research reveals molecular-level details into the syndrome’s lasting effects on inflammation and immune response in people with ME/CFS.

www.publichealth.columbia.edu/news/overact...

www.nature.com/articles/s44...

Very exciting to see a new NLRP3 inhibitor enter the clinic! Great work from BioAge Labs www.globenewswire.com/news-release...

An mRNA-based broad-spectrum antiviral inspired by ISG15 deficiency protects against viral infections in vitro and in vivo A human inborn error of immunity guided discovery and development of a prophylactic, mRNA-based antiviral.

Latest by us! An mRNA-based broad-spectrum antiviral inspired by ISG15 deficiency protects against viral infections in vitro and in vivo | Science Translational Medicine www.science.org/doi/10.1126/...

Systemic auto-inflammatory diseases, auto-immune diseases and immune deficiencies: From independent to overlapped diseases approach Systemic AutoInflammatory Diseases (SAIDs), AutoImmune Diseases (AIDs), and Primary Immune Deficiencies (PIDs) were formely considered independent, ev…

Adding to the conversation—in the same spirit, I think this recent paper is important:
🔗 www.sciencedirect.com/science/arti...

📌

RNA N-glycosylation enables immune evasion and homeostatic efferocytosis - Nature N-glycans on glycoRNAs prevent innate immune sensing of endogenous small RNAs, and the natural mechanism they use demonstrates how glycoRNAs exist on the cell surface and in the endosomal network with...

#GlycoPower! @vijayrathinam.bsky.social
@raflynn5.bsky.social @vinnieviruses.bsky.social &co show @nature.com that N-glycosylation of host small-RNAs present at cell surface prevents immune recognition by TLR3 and TLR7 upon apoptotic cells uptake avoiding autoinflammation!

Ethical and equitable considerations when establishing a diagnosis of an inborn error of immunity url: rupress.org/jhi/article/...

Systemic auto-inflammatory diseases, auto-immune diseases and immune deficiencies: From independent to overlapped diseases approach Systemic AutoInflammatory Diseases (SAIDs), AutoImmune Diseases (AIDs), and Primary Immune Deficiencies (PIDs) were formely considered independent, ev…

Adding to the conversation—in the same spirit, I think this recent paper is important:
🔗 www.sciencedirect.com/science/arti...

rheumatologists are often first in line, guiding care and ordering genetic panels or WES.

This feels like a natural opportunity to deepen collaboration and recognize the overlaps between clinical immunologists and rheumatologists.

As diagnostic frameworks for inborn errors of immunity continue to evolve, rheumatology plays a critical role.

In many scenarios—especially when systemic inflammation, autoimmunity, or autoinflammation is the first clue—

Longitudinal Analysis of Somatic Mosaicism and Clonal Hematopoiesis in Cryopyrin‐Associated Periodic Syndrome Objective Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory disease caused by gain-of-function mutations in NLRP3. Although somatic NLRP3 mosaicism is increasingly recognized, it ...

Longitudinal Analysis of Somatic Mosaicism and Clonal Hematopoiesis in Cryopyrin-Associated Periodic Syndrome

acrjournals.onlinelibrary.wiley.com/doi/epdf/10....

10 things you wish you knew about inflammatory caspases: a holistic review of their biochemistry, activation, and signalling Caspases are a family of cysteine proteases conserved across all multicellular life which play critical functions that range from cell death, inflammation and cellular differentiation. Caspases cleave...

www.jbc.org/article/S002...

The NLRP3 inflammasome in microglia regulates repetitive behavior by modulating NMDA glutamate receptor functions In this study, Jung et al. investigate the effect of excessive NLRP3-mediated neuroinflammation on synaptic functions and behaviors using Nlrp3D301N-conditional knockin mice. Strikingly, excessive NLR...

www.cell.com/cell-reports...