IMAGE Lab

Nice one congrats John et al!

Respiratory viral infections awaken metastatic breast cancer cells in lungs - Nature Mouse models show that respiratory infections from viruses such as influenza and SARS-CoV-2 can trigger metastasis of dormant breast cancer cells in the lungs, a finding supported by epidemiological d...

Out @nature.com led by @jdegregori.bsky.social Mercedes Rincon @roelvermeulen.bsky.social @jaguirreghisolab.bsky.social et al. in vivo mouse models & human data show resp. infections drive IL-6 dependent re-awakening of dormant cancer cells in lung.

So much to like about this paper! Congrats all!

Very excited at the chance to work with new people with new ideas in immunology! Really keen to hear from people from diverse backgrounds with different ways of thinking. International applicants seeking freedom to pursue BlueSky projects welcome. Come for the science. Stay for the vibe!
#immunosky

Now online in Cancer Discovery: AAnet Resolves a Continuum of Spatially-Localized Cell States to Unveil Intratumoral Heterogeneity - by Aarthi Venkat, Scott Youlten, Beatriz San Juan, Smita Krishnaswamy, Christine Chaffer, and colleagues doi.org/10.1158/2159...

Much obliged will do. 😊

😅

Yes please!

But sc data is noisy and nonlinear. AAnet takes archetype analysis to the next level by using an autoencoder to transform the data into a simplicial latent space. AAnet more accurately defines heterogeneity within cellular clusters & druggable transcriptional programs that drive heterogeneity. 3/3

Continuum of Gene-Expression Profiles Provides Spatial Division of Labor within a Differentiated Cell Type Single-cell gene expression reveals the diversity within a differentiated cell type. Often, cells of the same type show a continuum of gene-expression…

Cells exist in discrete cell states (clusters) but also cells show a continuum of gene expression (trajectory). @urialonlab.bsky.social first used archetype analysis to reconcile this paradox - the bioinformatic equivalent of wave-particle duality. This works if the ambient data space is linear. 2/3

Christine Chaffer, @skummerf.bsky.social at @garvaninstitute.bsky.social, Smita Krishnaswamy at Yale et al present AAnet a neural network for nonlinear archetype analysis that more accurately captures cell plasticity & learns the spatial organisation of the archetypes. What is the advance? 1/3

New Horizons for Multiple Sclerosis Therapy: 2025 and Beyond The advances achieved against multiple sclerosis (MS) represent one of the great success stories of modern molecular medicine. The development of therapies with increasing selectivity and safety, gui....

Very pleased to co-write this review with Bruce Cree and Steve Hauser on the future of #multiplesclerosis treatment

onlinelibrary.wiley.com/doi/10.1002/...

It was wonderful to meet with the #OCCAMS Consortium today on #WorldMSDay for an update on our study progress, as well as reviewing recent literature on the role of EBV in multiple sclerosis. Thanks to all participants for joining in the great discussions!
@garvaninstitute.bsky.social

YouTube video by Monty Python What Have The Romans... - Monty Python's Life of Brian

What have the National Institutes of Health ever done for us?

Thanks Kamila!

Evidence of innate lymphoid cell redundancy in humans - Nature Immunology The importance of human innate lymphoid cells to normal human physiology is unclear. Vivier and colleagues find that immunodeficient patients ‘rescued’ with normal bone marrow can recover their T cell...

Not sure if this is what you meant. DOCK8 deficiency (but not STAT3) is reported to have peripheral blood ILC3 defect which corrects after HSCT. In contrast, SCID patients may not reconstitute their NKs and ILCs after HSCT with no obvious health consequences suggesting they are dispensable.

Though every Cell paper is special, I occasionally get a paper that ✨delights✨ me from start to finish. These astute scientists found a unique opportunity to study an audacious snake venom enthusiast and uncovered antibodies that could serve as a broad antidote to snakebites. 🐍

Thanks Mauro! They make beautiful memories!

Macrophages direct location-dependent recall of B cell memory to vaccination @cellcellpress.bsky.social @ramadhenni.bsky.social @immunodealex.bsky.social
www.cell.com/cell/fulltex...

Thanks Cheri!

Thanks Jen!

Macrophages direct location-dependent recall of B cell memory to vaccination Subcapsular sinus macrophages in the draining lymph node help retain resident memory B cells in the subcapsular niche and promote their re-entry into secondary germinal centers. Boosting vaccines in t...

Vaccination in left arm, right arm, or both?? @labphan.bsky.social congrats and looking to you for the answer 😄

Macrophages direct location-dependent recall of B cell memory to vaccination: Cell www.cell.com/cell/fulltex...

Macrophages direct location-dependent recall of B cell memory to vaccination Vaccines generate long-lived plasma cells and memory B cells (Bmems) that may re-enter secondary germinal centers (GCs) to further mutate their B cell…

So location does matter & boosting on the same side may make a difference! Basic research can underpin clinical translation. Can't have one without the other! Thankful to all our funders especially NHMRC, ACRF & UNSW Scientia Program. Thank you for reading please check out our paper! End 🧵

Serum neutralising antibody levels against ancestral, Delta and Omicron variants.

This was associated with more rapid secretion of neutralising antibodies against the ancestral strain in the vaccine as well as Delta and Omicron variants. In agreement, there was more somatic hypermutation & antibody diversification in the boosted dLN compared to ndLN.

Flow cytometric analysis of fine needle biopsies from healthy participants with vaccine boost in the same compared to opposite arm.

Please note caveats about persistent GCs from the COVID mRNA vaccine (Turner, Ellebedy et al. Nature 2021). Regardless, we did see more GCs in the boosted dLN compared to ndLN

Experimental design of clinical study comparing boosting of the COVID mRNA vaccine in the same or opposite arm of healthy participants.

This was all done in inbred genetically modified mice using intravital microscopy. Could boosting the same versus opposite side make a difference in 'wildtype' 'outbred' humans? This is where the Kirby Institute team came into their own! In the clinical study they also sampled the LN by FNB!

Experimental design and enumeration of the recall response in non-draining lymph node that had been 'primed' with an irrelevant, non-cognate antigen.

What about the SSMs? To test if vaccine had 'primed' the dLN SSMs we synchronously immunised the ndLN with an irrelevant non-cognate antigen. Now when we boost the 'ndLN' with cognate antigen there was larger recall & more GCs, just like dLN! This effect was abolished by anti-CSF1R mAb blocking.

Heatmap and violin plots showing differentially expressed genes between memory B cells in the draining lymph node, non-draining lymph node and spleen and naïve B cells in the lymph node and spleen.

Rama did scRNAseq & showed that dLN Bmems were distinct from ndLN Bmems. Upregulated dLN genes were involved in cell adhesion, migration & localisation, BCR activation & GC formation. Upregulated ndLN genes were involved in cell migration, tissue residence & plasma cell vs GC differentiation.

Flow cytometric analysis showing impaired recall response and GC re-entry in the draining lymph node when subcapsular sinus macrophages are depleted with anti-CSF1R mAb.

Is this relative positioning of Bmems in relation to the SCS niche important? Boosting of the dLN led to bigger and better Ab responses with more GCs & affinity maturation compared ndLN. But when SSMs are depleted with anti-CSF1R this effect is abolished.

Rama used intravital microscopy to show that Bmems were positioned deeper in follicle ndLN vs dLN where they were largely confined to the SCS layer. Depletion of CD169+ SCS macrophages (SSMs) with blocking anti-CSF1R mAb led to relocalisation of dLN Bmems deeper in the follicle.

Memory B cells are reactivated in subcapsular proliferative foci of lymph nodes - Nature Communications Memory B cells need to be reactivated to produce high affinity antibody responses on subsequent antigen encounters. Here the authors show that memory B cells localise to lymph node subcapsular prolife...

We previously showed Bmems reside in a subcapsular sinus (SCS) niche in the draining lymph node (dLN). Antigen recall led to re-entry into 2˚GCs or plasma cell differentiation in subcapsular proliferative foci (SPF). But what about the non-draining lymph node (ndLN)?