Plasticity and lineage commitment of individual T<sub>H</sub>1 cells are determined by stable T-bet expression quantities.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38838155.
- Also identified by DOI 10.1126/sciadv.adk2693 and PMC identifier 11152138.
- Licence recorded as CC BY-NC.
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Abstract
T helper 1 (T<sub>H</sub>1) cell identity is defined by the expression of the lineage-specifying transcription factor T-bet. Here, we examine the influence of T-bet expression heterogeneity on subset plasticity by leveraging cell sorting of distinct in vivo-differentiated T<sub>H</sub>1 cells based on their quantitative expression of T-bet and interferon-γ. Heterogeneous T-bet expression states were regulated by virus-induced type I interferons and were stably maintained even after secondary viral infection. Exposed to alternative differentiation signals, the sorted subpopulations exhibited graded levels of plasticity, particularly toward the T<sub>H</sub>2 lineage: T-bet quantities were inversely correlated with the ability to express the T<sub>H</sub>2 lineage-specifying transcription factor GATA-3 and T<sub>H</sub>2 cytokines. Reprogramed T<sub>H</sub>1 cells acquired graded mixed T<sub>H</sub>1 + T<sub>H</sub>2 phenotypes with a hybrid epigenetic landscape. Continuous presence of T-bet in differentiated T<sub>H</sub>1 cells was essential to ensure T<sub>H</sub>1 cell stability. Thus, innate cytokine signals regulate T<sub>H</sub>1 cell plasticity via an individual cell-intrinsic rheostat to enable T cell subset adaptation to subsequent challenges.
Medical subject headings
- Th1 Cells
- T-Box Domain Proteins
- Cell Lineage
- Cell Differentiation
- Cell Plasticity
- Th2 Cells