David UsharauliMay 21

1/ 🧪 The Rudensky lab never shies away from using cutting-edge gene tech to study Tregs. Their latest approach? Reversible protein degradation via ubiquitination. 👀 #Immunology #Tregs #science #Foxp3

https://www.researchsquare.com/article/rs-6596747/v1

Temporal and Context-Dependent Requirements for the Transcription Factor Foxp3 Expression in Regulatory T Cells

Regulatory T (Treg) cells, expressing the transcription factor Foxp3, are obligatory gatekeepers of the immune responsiveness. While Foxp3 essential role in Treg l differentiation is well established, the mechanisms by which Foxp3 governs the Treg-specific transcriptional network remain incomplet...

Show threadDavid UsharauliMay 21
2/💡 They engineered a system to reversibly degrade Foxp3, the master regulator of Treg identity. This lets them test what happens when #Foxp3 protein vanishes in adult mice. 🔄🧬
Show threadDavid UsharauliMay 21
3/ Surprisingly, removing Foxp3 protein in adult Tregs didn't trigger immune chaos. 😲 Unlike in neonates, adult Tregs kept functioning.
➡️ Suggests the Treg program becomes self-sustaining over time. #ImmuneTolerance
Show threadDavid UsharauliMay 21
4/ ⌛ It took about 2 weeks for Tregs to “lock in” their identity after Foxp3 expression. After that, it ran on autopilot, no Foxp3 protein needed... unless something disturbs the system (e.g., tumors or lymphopenia). 🔁
Show threadDavid UsharauliMay 21
5/ 🤔 This raises 2 big questions:
1️⃣ If Foxp3 isn’t needed long-term, why do adult Tregs keep expressing it?
2️⃣ Could some Tregs lack Foxp3 protein and still function normally? Are we mislabeling? #Immunology #TregMystery
Show threadDavid Usharauli
Generally speaking, this high-tech approach to biology isn’t intuitive but it may yield results through the sheer number of observations. #Immunology
May 21 at 7:52pmWeb