Abdelaal, Gherardin, Rossjohn, @waelawad.bsky.social et al show that host-generated riboflavin breakdown products can bind to the immune protein MR1. Unlike microbial vitamin B precursors, these compounds reduce MR1 surface levels & may dampen #MAIT cell immune activation rupress.org/jem/article/...

In @jem.org, Abdelaal, @waelawad.bsky.social et al show that host-generated riboflavin breakdown products can bind to the immune protein MR1. Unlike microbial vitamin B precursors, these compounds reduce MR1 surface levels & may dampen #MAIT cell immune activation rupress.org/jem/article/...

The antigen-presenting molecule MR1 binds host-generated riboflavin catabolites @jem.org @waelawad.bsky.social @monashuniversity.bsky.social
rupress.org/jem/article/...

Mitochondria regulate MR1 protein expression and produce self-metabolites that activate MR1-restricted T cells | PNAS Mitochondria coordinate several metabolic pathways, producing metabolites that influence the immune response in various ways. It remains unclear wh...

Mitochondria produce nucleobase ligands for T cells.
Our recent paper was published today in PNAS.

Mitochondria regulate MR1 protein expression and produce self-metabolites that activate MR1-restricted T cells | PNAS www.pnas.org/doi/10.1073/...

Our recent review on MR1-MAIT axis
Molecular Insights Into MR1-Mediated T Cell Immunity: Lessons Learned and Unanswered Questions

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

Scientists discover exactly how smoking can damage the lungs Although smoking rates in the UK are falling, the country's growing population means roughly 6.4million Brits are estimated to be hooked on the habit.

www.dailymail.co.uk/health/artic...

Great to see this work published! Congrats to Wael, Jamie and coauthors 🎉

Wael Awad, Jemma Mayall, Weijun Xu, Jamie Rossjohn and colleagues show that cigarette smoke contains a diverse mix of chemicals that bind the antigen-presenting protein MR1 and modulate MAIT cell function in the lung through diverse mechanisms. https://buff.ly/3PG6u6v

Thanks Lauren and congratulations for you too

This illustration by Erica Tandori explores how smoke components in cigarette & e-cigarette smoke obscures critical molecules like smoke-binding ligands & MR1 complexes, disrupting T-cell responses

This discovery is a key step in understanding how #Cigarette smoke disrupts the immune system and contribute to deadly lung disease.

Interestingly, mice lacking MAIT cells (MR1 deficiency) demonstrated partially protection against the development of cigarette-induced COPD.
Thus, #cigarette smoking can impair #MAIT functions, and potentially contribute to infection susceptibility and disease exacerbations.

Then, we discovered via mice studies that Chronic CS exposure altered MAIT cell phenotype and function in vivo, which increases susceptibility to influenza A virus infection and exacerbates COPD.

Protein crystallography was next used to ascertain the molecular basis of MR1 binding of CS components, and we found that these compounds bound the MR1 ligand binding pocket via forming a covalent interaction with Lys-43, a key residue of MR1.

These adverse effects of smoking on immunity not only occur in active smokers, but also in those exposed to smoke passively in contaminated environments and may persist for decades after exposure has ended. These CS ligands found to moderately impair MAIT activity ex vivo.

We the identified components of CS that MR1 detect using in silico and cellular assays. This includes nicotinaldehyde, thirdhand CS component, which give the smell of the smoke on clothes, cars, inside the house and including flavourings in cigarettes, e-cigarettes.

First, we discovered that CS extract changes
MAIT cell activation in vitro and increases MR1 surface expression. We suspected that some of the more than 20,000 chemicals present in cigarette smoke that smokers inhale might bind to MR1 and influence the T cells in the lungs

Finally, published
@JExpMed
after a decade of work.
Through multidisciplinary approaches, we found that components of #cigarrete & #vaping smoke (CS) modulate #MR1- #MAIT cells axis in the lung with a major implication for COPD, the third leading cause of death worldwide
See 🧵

#PressRelease 📰 Australian researchers have discovered that multiple chemicals found in cigarette smoke & e-cigarettes alter the function of a key type of immune cell found in the lungs.
In our News Release: https://buff.ly/3C9kmmH
Original paper in JEM: https://buff.ly/3PG6u6v

Cigarette smoke chemicals bind MR1 and modulate MAIT cell function in the lung through diverse mechanisms, impacting their ability to respond to respiratory infections and potentially contributing to disease
doi.org/10.1084/jem....