The Gene Lay Institute of Immunology and Inflammation

Cellular & spatial profiling of fibrosis in Crohn's disease provides new insights into the mechanisms involved.
From the lab of our Vice Director @thexavierlab.bsky.social in collaboration with #SmillieLab.
Study led by #LingjiaKong @broadinstitute.org

Scientists discover network of cells and genes involved in Crohn’s disease complication Spatial mapping reveals genes contributing to fibrosis, or scarring, in the gut, laying the foundation for better treatments.

Dr. Ramnik Xavier and Dr. Christopher Smillie from the @broadinstitute.org analyzed individual cells from the intestinal tissue of #Crohns disease patients, measuring gene activity and mapping the cells’ location: bit.ly/4nwuf0s

📃 @natgenet.nature.com: go.nature.com/45UEWDH

Single-cell and spatial transcriptomics of stricturing Crohn’s disease highlights a fibrosis-associated network @natgenet.nature.com @thexavierlab.bsky.social
www.nature.com/articles/s41...

@kepauken.bsky.social, Markson, Sharpe et al. @harvardmed.bsky.social show that when PD-1–expressing and PD-1 knockout CD8+ T cells are within the same tumor microenvironment, both cell types exhibit similarly enhanced functions. rupress.org/jem/article/...

🚨 New study from the lab of our Vice Director, Arlene Sharpe, led by @kepauken.bsky.social & #SamuelMarkson in @jem.org.
PD-1 regulates tumor-infiltrating CD8+ T cells in both a cell-intrinsic & a cell-extrinsic fashion🧪

PD-1 regulates tumor-infiltrating CD8+ T cells in both a cell-intrinsic and a cell-extrinsic fashion Pauken and Markson et al. show that when PD-1–expressing and PD-1 knockout CD8+ T cells are within the same tumor microenvironment, both cell types exhibit

Excited to announce that my final co-first author publication from my postdoctoral training with Dr. Arlene Sharpe was published in @jem.org today! Thank you to everyone involved! Check out our new findings on the importance of cell extrinsic consequences after PD1 loss!

rupress.org/jem/article-...

Eggerthella lenta Produces a Cryptic Pro-inflammatory Lipid Eggerthella lenta is both one of the most studied and least understood members of the human gut microbiome. Most of the interest in this Gram-positive anaerobe originates from multiple robust associations of its population with a variety of autoimmune diseases, perhaps most notably inflammatory bowel disease (IBD). The links between bacteria and inflammation are only partially known. Inflammation is driven by Th17 cells and their inflammatory cytokine IL-17, and the population of these cells is promoted by a transcription factor, RORγt. Bacterial metabolites appear to activate RORγt in a cell- and antigen-independent fashion, but the metabolites and their activating mechanism are unknown. This report describes an assay-driven search for pro-inflammatory metabolites from E. lenta that revealed a plasmalogen-triggered plasmalogen pair that forms a single molecule signal transduction device. Small electrophiles characteristic of inflammatory environments react with the plasmalogen’s sensitive vinyl ether moiety to create a lipid signal, a lysoglycoglycerolipid that upregulates the inflammatory cytokines TNF-α and IL-6 through a TLR receptor. This provides a molecular mechanism that allows E. lenta to upregulate inflammatory responses in a cell- and antigen-independent fashion. This molecular mechanism is similar to an endogenous signaling system that upregulates RORγt through a triggered mammalian plasmalogen signal, 1–18:0-lysophosphatidylethanolamine.

This finding suggests that molecular patterns could be more useful categories for microbiome-driven immune regulation than taxonomy. (2/2)

Read the study in JACS – pubs.acs.org/doi/10.1021/...

@broadinstitute.org
@mgbresearch.bsky.social

In our latest collab w/the Clardy Lab
@HarvardMed to mine microbial metabolites for immunomodulators, we identified how Eggerthella lent—one of the most studied & least understood members of the human gut microbiome—upregulates inflammatory responses in a cell- & antigen- independent fashion. (1/2)

<em>Immunology & Cell Biology</em> | ASI Journal | Wiley Online Library In this article, we have analyzed the serum proteome and metabolome in inflammatory bowel disease patients being treated with the anti-α4β7 integrin therapeutic agent vedolizumab. The pretreatment bi...

Check out our recent work with John Rioux and the iGenoMed Consortium! Serum proteomic and metabolomic profiling in #IBD patients initiating vedolizumab identified pro-inflammatory analytes associated with treatment response.

onlinelibrary.wiley.com/doi/10.1111/...

Our annual symposium on Immunity & Inflammation in Disease & Tissue is on again on August 6th.
🎙️Looking forward to talks from #RafiAhmed, #RichardFlavell, @thefuchslab.bsky.social, #BanaJabri & #LawrenceSteinman.
Joseph B. Martin Conference Center, Boston MA

Barcoded viral tracing identifies immunosuppressive astrocyte–glioma interactions - Nature Using viral barcode tracing to detect interactions between glioblastoma cells and non-malignant astrocytes in patient samples, investigators discovered a pathway that reduces tumour-specific immunity ...

Our newest paper studying immunosuppressive astrocyte-GBM interactions using RABID-seq is out in ‪@nature.com today! Congrats to Brian Andersen and Camilo Faust Akl!
www.nature.com/articles/s41...

Single-cell and spatial transcriptomics of stricturing Crohn’s disease highlights a fibrosis-associated network - Nature Genetics Single-cell and spatial transcriptomics analysis of stricturing Crohn’s disease highlights cellular heterogeneity in fibrotic tissue and identifies neighborhoods of fibroblasts and immune cells contri...

Very excited to share our latest work in @NatureGenet with the Smillie lab: a spatial transcriptomics atlas of stricturing #Crohns disease that offers new insights into mechanisms driving fibrotic complications in chronic gut inflammation...(cont.)
www.nature.com/articles/s41...

Have you registered yet for #ReThinkNeuroimmunology in October?
Speakers include @aleksdelab.bsky.social @labschaefer.bsky.social @annamolofskylab.bsky.social @itchdoctor.bsky.social @becherlab.bsky.social @gocastelobranco.bsky.social @miriammerad.bsky.social @kuchroolab.bsky.social & more

Detection of astrocyte epigenetic memory in in vitro systems, experimental autoimmune encephalomyelitis and multiple sclerosis samples We recently described astrocyte pro-inflammatory epigenetic memory based on multiple complementary in vivo and in vitro studies, and the analysis of multiple sclerosis samples. Based on bioinformatic ...

New pre-print from our lab here:
www.biorxiv.org/content/10.1...

The glycolytic reaction PGAM restrains Th17 pathogenicity and Th17-dependent autoimmunity @cp-cellreports.bsky.social @kuchroolab.bsky.social
www.cell.com/cell-reports...

The glycolytic reaction PGAM restrains Th17 pathogenicity and Th17-dependent autoimmunity Wang et al. identify phosphoglycerate mutase (PGAM) as a negative regulator of pathogenic Th17 cell differentiation, contrary to other glycolytic enzymes. PGAM inhibition suppresses a regulatory progr...

The glycolytic enzyme, phosphoglycerate mutase (PGAM), is a key metabolic regulator suppressing Th17 cell pathogenicity & autoimmunity.
Led by Chao Wang, Allon Wagner & Johannes Fessler, with #Yoseflab, our study is now published @cp-cellreports.bsky.social 🔗 www.cell.com/cell-reports...

Grad student, #RockyBarilla was responsible for driving this huge effort. Well done!

Bacterial sphingolipids delivered by outer membrane vesicles persist within mammalian immune cells and promote IL-10 secretion via the mevalonate pathway
www.cell.com/cell-host-mi...
@thexavierlab.bsky.social @cp-cellhostmicrobe.bsky.social

(1/6) Our latest paper in ‪@cp-cellhostmicrobe.bsky.social‬ shows that sphingolipids in Bacteroides outer membrane vesicles (OMVs) induce a tolerogenic host cell response through the cholesterol biosynthesis pathway.
www.cell.com/cell-host-mi...

Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense Enteric nervous system (ENS)–derived neuropeptides modulate immune cell function, yet our understanding of how inflammatory cues directly influence enteric neuron responses during infection is conside...

Out now in @Science! We and the @kuchroolab.bsky.social described responses of enteric neurons to inflammatory cues during infection, showing that primary sensory neurons detect type 2 cytokines, balance neuropeptides, and influence site-specific immunity

www.science.org/doi/10.1126/...

Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense
www.science.org/doi/10.1126/...
@science.org @kuchroolab.bsky.social @thexavierlab.bsky.social

We show that Th2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven clearance of gut pathogens🪱🪱.

Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense Enteric nervous system (ENS)–derived neuropeptides modulate immune cell function, yet our understanding of how inflammatory cues directly influence enteric neuron responses during infection is conside...

🚨New paper with @thexavierlab.bsky.social @science.org on the critical role of 🔄neuroimmune crosstalk in immune defense in the gut🪱🪱.
🧪@genelayinstitute.bsky.social @mgbresearch.bsky.social @harvardmed.bsky.social @broadinstitute.org
www.science.org/doi/10.1126/...

Glioblastoma-instructed astrocytes suppress tumour-specific T cell immunity - Nature A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve o...

New research from @quintanalabhms.bsky.social show how glioblastoma co-opts TRAIL-positive astrocytes to suppress anti-tumor T cell function. Now published @nature.com
www.nature.com/articles/s41...

So great that Brenda & Jason gave us daily recaps of their favorite talks at #AAI2025 via @immunologypodcast.com.
🌟Episode 5 features a talk by Ana Anderson on how opioids drive immunosuppression in T cells in cancer.
Listen to all the episodes for highlights from the🧪 @aai.org conference👇

Immune-system strategy used to treat cancer may help with Alzheimer’s — Harvard Gazette Turning off checkpoint molecules freed microglia to attack plaques in brain, improved memory in mice.

A new study raises the odds that a strategy already successful against some cancers may be deployed against Alzheimer’s.
From @kuchroolab.bsky.social and colleagues, co-first authors Kimitoshi Kimura and @ayshwaryas.bsky.social
news.harvard.edu/gazette/stor...

Insightful review on overlapping & distinct immune-related mechanisms of Alzheimer's disease & age-related macular degeneration, by Oleg Butovsky & Neta Rosenzweig. Now out in the special issue on The Neuro-immune Axis @cp-immunity.bsky.social

Review @cp-immunity.bsky.social
Alzheimer’s disease and age-related macular degeneration: Shared and distinct immune mechanisms
www.cell.com/immunity/ful...

Beyond T cell exhaustion: TIM-3 regulation of myeloid cells We provide a comprehensive review of 20 years of research on TIM-3 functions in myeloid cells and T cell exhaustion.

@dixon-lab.bsky.social, Gonzalo Fernandez Lahore, & @kuchroolab.bsky.social discuss the emerging roles for #TIM3 in regulating #MyeloidCell #immune responses!

Immune-system strategy used to treat cancer may help with Alzheimer’s — Harvard Gazette Turning off checkpoint molecules freed microglia to attack plaques in brain, improved memory in mice.

Our research on how the immune checkpoint TIM-3 regulates microglia & Alzheimer's disease highlighted in the @harvard.edu Gazette 👇
🧪
news.harvard.edu/gazette/stor...