Chrysothemis Brown
@chrysothemisbrown.bsky.social
Pediatrician | Immunologist @MSK Cancer Center | Freeman Hrabowski Scholar, HHMI
www.thebrownlaboratory.com
www.thebrownlaboratory.com
Thank you for the lovely write up!
July 30, 2025 at 11:58 PM
Thank you for the lovely write up!
I will connect you to Vanja! She’s not on Bluesky - drop me an email and I will loop her in!
May 22, 2025 at 2:42 AM
I will connect you to Vanja! She’s not on Bluesky - drop me an email and I will loop her in!
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
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
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....
www.nejm.org/doi/full/10....
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 ...
www.nejm.org
May 21, 2025 at 6:24 PM
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....
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
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/
May 21, 2025 at 6:24 PM
We now show that TCs, specifically TC IV, instruct food-specific pTreg differentiation and oral tolerance. 3/
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...
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...
www.nature.com
May 21, 2025 at 6:24 PM
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...