Reinhard Hinterleitner

Our findings reveal a protective role for GSDMC in intestinal epithelial cells during helminth infection- and expand the function of gasdermins beyond classical roles in pyroptosis and cytokine release

Using a clever approach (Yi-Nan), we showed that inserting a single amino acid within the lipid binding motif (to mimic pyroptotic gasdermins) enhances GSDMC oligomerization and increases its ability to induce cell death

Mechanistically, cleaved GSDMC doesn’t localize to the plasma membrane as typical gasdermins do (eg GSDMD) Rather, GSDMC targets Rab7+ vesicles (late endosomes) leading to lipid droplet accumulation, which in turn promotes goblet cell hyperplasia and type 2 immune responses

Similar to findings by Drs Hai-Bin Ruan and Xiaoyu Hu, we observed that GSDMC activation does NOT drive epithelial cell (IEC) death. Instead, we found that intestinal GSDMC is not cleaved by caspases, but DIRECTLY by the cysteine protease Cathepsin S generating a functional GSDMC-Nter

GSDMC is barely expressed in the intestine but is induced 100-fold and cleaved (activated) in response to type-2 triggers like helminth infection or colonization by the commensal protist Tritrichomonas.

Big thank you to our amazing collaborators @meisellab.bsky.social @jmoltke.bsky.social and Suhong Xu #GSMC #Helminth #Tritrichomonas #type-2-immunity

Gasdermin C cleavage by Cathepsin S modulates Rab7 vesicles in intestinal epithelial cells to amplify anti-helminth immunity Pandey et al. identify Cathepsin S (CTSS) as the direct protease that cleaves Gasdermin C (GsdmC) in the intestine. Type 2 immune-promoting microbes trigger CTSS-dependent GsdmC activation in intestin...

Excited to share our new publication in collaboration with Yi-Nan Gong: Gasdermin C cleavage by Cathepsin S modulates Rab7 vesicles in intestinal epithelial cells to amplify anti-helminth immunity: Immunity www.cell.com/immunity/ful...

The Global Grants for Gut Health are now open. If your research explores how nutrition affects the gut #microbiome or barrier function, you may be eligible to apply for one of three grants each offering up to USD$100K. Apply here: go.nature.com/4kb9cO1 #Academicsky 🍎📃

Waves crashing on a rocky landscape.

Welcome to #InnovationsSymposium2025! We’re excited to be together again—this year on the beautiful island of Oʻahu—to hear the latest #IBD research and encourage dialogue and connections that continue to move the work forward.

Exercise-induced microbiota metabolite enhances CD8 T cell antitumor immunity promoting immunotherapy efficacy Exercise enhances antitumor immunity and immunotherapy effectiveness by increasing microbiota-derived formate, which boosts CD8 T cell function and may serve as a biomarker of melanoma suppression.

Our lab just completed a +6 year #marathon, describing for the first time that the #microbiome is critical for #exercise - induced increases in antitumor CD8 T cell immunity and improved of #cancer #immunotherapy.
www.cell.com/cell/fulltex...

Microbiome mismatches from microbiota transplants lead to persistent off-target metabolic and immunomodulatory effects Fecal microbiota transplants (FMTs) may not always effectively restore small bowel microbiota due to regional differences in gut environments, potentially causing unintended effects on metabolism and ...

The unintended consequences of a gut microbiome transplant
www.cell.com/cell/abstrac...

Immunoglobulin A controls intestinal virus colonization to preserve immune homeostasis
www.cell.com/cell-host-mi...

Let's not forget that apart from science advocacy the Rauch lab also does kick-ass science!
Together with the @psmitchej.bsky.social and Tait Wojno labs, we show that #tuftcells can induce specific protective signaling after recognition of intracellular bacterial infection via the #inflammasome!

Cathedral of Learning with crowd gathered on Schenley Plaza grass in foreground

Stand Up for Science Rally in Pittsburgh

#KSHostMicrobe25 in beautiful Banff-such an awesome meeting. Was great to talk at the @keystonesymposia.bsky.social about exciting work from the lab about how we can take advantage of the microbiota metabolites to improve cancer immunotherapy efficacy
#microbiota #immunometabolism #cancer

Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda Enteric viral infections are a major public health problem in newborns. Ramirez Reyes et al. find that the immature intestinal epithelium of newborn mice is developmentally programmed for the homeosta...

Homeostatic antiviral protection of the neonatal gut epithelium by interferon lambda: Cell Reports www.cell.com/cell-reports...

Newborns lack immune memory to viral pathogens, so wouldn't it make sense to pre-emptively turn on antiviral defenses in barrier tissues such as the intestine at birth?

Scratching promotes allergic inflammation and host defense via neurogenic mast cell activation Itch is a dominant symptom in dermatitis, and scratching promotes cutaneous inflammation, thereby worsening disease. However, the mechanisms through which scratching exacerbates inflammation and wheth...

Why scratching makes a rash worse and a potential benefit to scratching--it reduced S. aureus on skin. Andrew Liu's paper from our lab is out now at #science #neuroimmune #immunology www.science.org/doi/10.1126/...

Don't miss your chance to showcase your research with a poster presentation! Submit by Jan. 28, 11:59pm MST. Be part of an exciting gathering with experts like @institutimagine.bsky.social, @reisesousalab.bsky.social and many others this February in Banff, Canada. hubs.la/Q032JT3R0 #KSHostMicrobe25

Limosilactobacillus reuteri - a probiotic gut commensal with contextual impact on immunity The gut microbiome plays a key role in human health, influencing various biological processes and disease outcomes. The historical roots of probiotics are traced back to Nobel Laureate Élie Metchni...

was a joy to write review about the systemic immunoregulatory functions of L. reuteri with @pitt-pmi.bsky.social student Amanda and postdoc Daphne. check it out. www.tandfonline.com/doi/full/10....

Congrats @cicacanesso.bsky.social !

Ever wondered how gut microbes control immune responses at extra-intestinal locations?
Here #theonlylabever reports how a gut protozoan commensal shapes pulmonary immunity to exacerbate asthma and limit the dissemination of mycobacteria.
@cellpress.bsky.social ⬇️(1/x)
www.cell.com/cell/fulltex...

Postdoctoral Fellow - Moltke Lab Post a job in 3min, or find thousands of job offers like this one at jobRxiv!

We're hiring! Funded postdoctoral position available in the Moltke Lab. 79k starting salary and access to a fellowship program in the Institute for Translational Immunology that offers both academic and industry training tracks. Details here: jobrxiv.org/job/universi...

Today we report that an engineered skin bacterium, swabbed gently on the head of a mouse, can unleash a potent antibody response against a pathogen. Could lead to topical vaccines that are applied in a cream. @djenetbousbaine.bsky.social led the charge... @natureportfolio.bsky.social 1/55

1/23 Big news for the #ObenaufLab! So excited to finally share our new study providing another puzzle piece, why immunotherapy fails in many tumors, now out in @Nature 🧵👇 www.nature.com/articles/s41...

Spatially restricted immune and microbiota-driven adaptation of the gut - Nature Intestinal regionalization is characterized by robust and resilient structural cell states and the intestine can adapt to environmental stress in a spatially controlled manner through crosstalk betwee...

1/ Keen to share the story of my postdoc research out in @natureportfolio.bsky.social! We built a massive resource characterizing the spatial landscape of the gut—and yes, we dug deep into the biology too. If you’ve got a minute, let me walk you through the story. 🧵👇
www.nature.com/articles/s41...

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