🧪 We also saw gut-specific transcriptional remodeling in Naive B cells and Tregs with upregulation of IFN-γ, chemokine, and T cell migration pathways.

Again, none of these were present in the blood 🥲

🧵 8/10

🔬 In terms of cell type abundance, circulating classical monocytes were negatively associated with inflammation, while all the other inflammation-related changes were gut-restricted.

🧬 Reinforcing the tissue-restricted nature of Crohn's inflammation.

🧵 7/10

🧠 CD4⁺ ex-Trms were enriched for IFN-γ signaling, while the pro-inflammatory CD4⁺ subset was enriched for TNFR2 and interleukin signaling.

Many of these inflammation-associated genes were also found in intestinal Tregs and macrophages — two key IBD players.

🧵 6/10

📈 More importantly ex-Trms were the only blood population whose gene expression correlated with gut inflammation, as measured by the TI-SES-CD scores.

👉These signatures were also shared with their intestinal counterparts.

🧵 5/10

👀 These ex-Trms were also present in public PBMC scRNA-seq datasets - across IBD, healthy donors, and other inflammatory conditions.

🧵 4/10

🔥 We discovered a rare subset of circulating T cells with Trm-like features (aka ex-Trms).

This included CD8⁺, CD4⁺, and a pro-inflammatory CD4⁺ subset expressing KLRB1 and CCR5, previously seen in the gut.

🧵 3/10

🧬 We performed single-cell RNA-seq on paired ileum and blood samples from 125 CD patients with matched endoscopy scores (TI-SES-CD), capturing shared and tissue-specific immune states.

🧵 2/10

Today, I got the opportunity to present at #ISCBLA2024 about how we are using single-cell to identify circulating and tissue specific signatures in Crohn's disease 👩🏻‍💻