Chrysothemis Brown

Antigen-presenting cells as arbiters of mucosal tolerance and immunity Nature Immunology - Brown and colleagues review the heterogeneity of mucosal antigen-presenting cells that orchestrate T cell immunity to intestinal antigens.

Excited to share our review on Thetis cells and dendritic cells, and their roles in mucosal immunity and tolerance @natimmunol.nature.com rdcu.be/eLtB1

Early Life Immune Development and Function   - IMMUNOLOGY2026™ Time: 8:00 - 11:30 AM Chairs: Chrysothemis C. Brown, Memorial Sloan Kettering Cancer Ctr., USA Petter Brodin, Imperial Col. London and Karolinska Inst., GBR, SWE

The American Association of Immunologists AAI meeting will be in Boston, April 15-19, 2026. Come join me and @chrysothemisbrown.bsky.social at this exciting Symposium on Early life immune development. Submit your abstracts by October 15th! immunology2026.aai.org/session/earl...

Thank you for the lovely write up!

Thank you for the lovely write up! @mskcancercenter.bsky.social

Yep...& senior author of one,
@chrysothemisbrown.bsky.social, will be at www.emds2025.com in Edinburgh 🏴󠁧󠁢󠁳󠁣󠁴󠁿 in Sept. to discuss their work. So, if you're interested in RORgt+ APC, or APC more generally, EMDS2025 is for you!

Abstract deadline: TODAY.

@britsocimm.bsky.social @natrevimmunol.nature.com

Thank you!!

I will connect you to Vanja! She’s not on Bluesky - drop me an email and I will loop her in!

Thank you!

A huge thanks to all of the Brown Lab, an exceptional team effort from Vanja, Yollanda, Zihan Zhao, Blossom Akagbosu, and our collaborators, Tyler Park, Christina Leslie, and funders @mathersfoundation.bsky.social @niaidnews.bsky.social, and PICI

Although these pro-inflammatory T-helper cell lineages represent a small fraction of OVA-specific Treg cells in wildtype mice, impaired pTreg cell differentiation led to enhanced effector T cell responses, highlighting the importance of balance between Treg and Teff cells. 15/

Finally, what do cDCs do when they present food antigens? We show that cDC1s promote food-specific TH1 differentiation, while cDC2s promote TFH differentiation. 14/

We show that TC IV numbers peak during the peri-weaning period and then rapidly decline. This wave of TCs is associated with a 7 fold-increase in the proportion of food-specific pTreg cells, suggesting that TC abundance determines the window of opportunity for oral tolerance 13/

Randomized Trial of Peanut Consumption in Infants at Risk for Peanut Allergy | NEJM The prevalence of peanut allergy among children in Western countries has doubled in the past 10 years, and peanut allergy is becoming apparent in Africa and Asia. We evaluated strategies of peanut ...

A landmark clinical trial - the LEAP study - showed that early introduction of peanuts reduced the risk of peanut allergy by 80%. What underlies this window of opportunity for tolerance to food? 12/

www.nejm.org/doi/full/10....

Parallel and recent studies from the labs of Daniel Mucida, Dan Littman, Marco Colonna and Jay Gardner have similarly identified a role for RORγt+ APCs in food-specific pTreg differentiation and oral tolerance in adult mice. So what's special about the weaning period? 11/

Gut lymph nodes are critical for oral tolerance suggesting that these lymph nodes harbor a unique population of tolerogenic APCs. Excitingly, we found that TC IV are enriched in mesenteric lymph nodes, and virtually absent in non-gut lymph nodes. 10/

These mice were able to generate food-specific pTreg cells, indicating that TC IV is the pTreg-inducing subset. 9/

To address the role of Aire+ TCs in pTreg differentiation we generated a new mouse model to selectively ablate RORγt+Aire+ cells. These mice have a specific loss of Aire+ TCs (TC I and TC III) but TC IV numbers are not impacted. 8/

However, TC III express low levels of ITGB8, as well as Aire, and other studies have suggested that RORγt+ extra-thymic Aire-expressing cells (RORγt-eTACs) might be responsible for pTreg differentiation. 7/

Deletion of MHCII or Itgb8 expression by TCs abolished food-specific pTreg differentiation. Since TC IV express the highest levels of ITGB8, and were the only subset to acquire labeled ovalbumin, we suspected that TC IV was the pTreg-inducing subset. 6/

Vanja and Yollanda started with a simple experiment – feeding mice fluorescently-labeled ovalbumin and seeing which cells in gut lymph nodes take up the protein. classical dendritic cells, they observed uptake by a specific subset of Thetis cells – TC IV. 5/

Although oral tolerance is often studied in adult mice, food allergies typically present in infancy when the immune system encounters food antigens for the first time. We therefore decided to study how tolerance is established during weaning. In mice this equates to day 12-18. 4/

We now show that TCs, specifically TC IV, instruct food-specific pTreg differentiation and oral tolerance. 3/

Novel antigen-presenting cell imparts Treg-dependent tolerance to gut microbiota - Nature Single-cell transcriptomic and epigenetic analysis has enabled the identification of Thetis cells, a class of RORγt+ antigen-presenting cells with a key role in the differentiation of commensal microb...

Three years ago, we identified a new lineage of RORγt+ antigen-presenting cells, Thetis cells, that encompass four subsets (TC I-IV). We showed that ITGB8+ TCs regulate tolerance to the gut microbiota by instructing pTreg differentiation 2/ www.nature.com/articles/s41...

A wave of Thetis cells imparts tolerance to food antigens early in life Within the intestine, peripherally-induced regulatory T (pTreg) cells play an essential role in suppressing inflammatory responses to food proteins. However, the identity of antigen-presenting cells (...

Excited to share our study describing a role for a subset of Thetis cells, TC IV, in tolerance to food antigens. A team effort led by Vanja Cabric and Yollanda Parisotto
www.science.org/doi/10.1126/...

Memorial Sloan Kettering Cancer Center Careers Let’s change the way the world treats cancer Our multi-disciplinary teams work together to provide exceptional patient care, develop innovative research, and deliver outstanding educational programs.

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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...