T-bet marks contact-capable regulatory T cells embedded within Th1-dendritic cell networks in skin-draining lymph nodes
- 1The Ohio State University
Abstract
Regulatory T cells (Tregs) adapt to inflammatory environments while preserving Foxp3-dependent suppressive identity. In type 1 inflammation, Tregs can upregulate T-bet, but whether T-bet Tregs represent a stable regulatory subset or exhibit plasticity toward an effector-like state remains incompletely understood. To probe the positioning and interactions of T-bet Tregs during type 1 inflammation, we performed live lymph node section microscopy in T-bet-ZsGreen Foxp3-RFP dual-reporter mice during a subcutaneous complete Freunds adjuvant (CFA) challenge. T-bet Tregs accumulated rapidly in the draining lymph nodes within 24 hours, coincident with the appearance of T-bet dendritic cells (DCs) and Th1-like CD4 T cells. Analysis of lymph node sections revealed that T-bet Tregs were incorporated into Th1-DC contact networks, displaying increased contact frequency and contact volume compared with T-bet- Tregs. In parallel, flow cytometric analysis of the immune response showed that T-bet Tregs maintained a stable regulatory profile distinct from T-bet effector T cells, with retained high expression of Foxp3 and regulatory-associated surface molecules including FR4, CD25, Nrp-1, CD39, and GARP. They also expressed elevated adhesion and activation-associated molecules, including LFA-1, ICOS, PD-1, CD44, and CD103 compared with T-bet- Tregs, and were enriched for CD103 cells across the inflammatory time course. Adoptive transfer studies further showed that pre-existing T-bet expression enhanced recovery of antigen-specific Tregs from CFA-draining lymph nodes in a context-dependent manner, whereas T-bet expression did not confer a unique advantage in canonical in vitro suppression of Th1 proliferation. Together, these findings identify T-bet Tregs as a contact-capable regulatory subset embedded within early Th1-DC networks during the priming phase of type 1 inflammation rather than a destabilized or effector-converted Treg population.
Related
- Melanoma suppresses galectin-9-glycan axis in dendritic cells and galectin-9 restoration limits T regulatory cell expansion
- Stochastic Dynamics of Large-Scale Motif-Embedded Spiking Neuronal Networks
- mTOR disrupts cerebrovascular RNA regulatory networks in Alzheimers disease
- Anthocyanins in woody ornamental plants: biosynthesis, regulatory networks, and trade-offs in stress adaptation
- Cross-regulatory sRNA networks shape adaptive stress responses in Staphylococcus aureus: RsaC and RsaOI regulate galactose metabolism and cell wall homeostasis
BibTeX
@misc{priddy2026tbet,
title = {{T-bet marks contact-capable regulatory T cells embedded within Th1-dendritic cell networks in skin-draining lymph nodes}},
author = {A. H. Priddy and M. P. Maz and O. Kamenyeva and J. Kabat and E. M. Shevach and M. Akkaya and B. Akkaya},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.756696},
url = {https://www.biorxiv.org/content/10.64898/2026.10.05.756696v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - T-bet marks contact-capable regulatory T cells embedded within Th1-dendritic cell networks in skin-draining lymph nodes
AU - A. H. Priddy
AU - M. P. Maz
AU - O. Kamenyeva
AU - J. Kabat
AU - E. M. Shevach
AU - M. Akkaya
AU - B. Akkaya
PY - 2026
DA - 2026/10/05
PB - bioRxiv
DO - 10.64898/2026.10.05.756696
UR - https://www.biorxiv.org/content/10.64898/2026.10.05.756696v1
AB - Regulatory T cells (Tregs) adapt to inflammatory environments while preserving Foxp3-dependent suppressive identity. In type 1 inflammation, Tregs can upregulate T-bet, but whether T-bet Tregs represent a stable regulatory subset or exhibit plasticity toward an effector-like state remains incompletely understood. To probe the positioning and interactions of T-bet Tregs during type 1 inflammation, we performed live lymph node section microscopy in T-bet-ZsGreen Foxp3-RFP dual-reporter mice during a subcutaneous complete Freunds adjuvant (CFA) challenge. T-bet Tregs accumulated rapidly in the draining lymph nodes within 24 hours, coincident with the appearance of T-bet dendritic cells (DCs) and Th1-like CD4 T cells. Analysis of lymph node sections revealed that T-bet Tregs were incorporated into Th1-DC contact networks, displaying increased contact frequency and contact volume compared with T-bet- Tregs. In parallel, flow cytometric analysis of the immune response showed that T-bet Tregs maintained a stable regulatory profile distinct from T-bet effector T cells, with retained high expression of Foxp3 and regulatory-associated surface molecules including FR4, CD25, Nrp-1, CD39, and GARP. They also expressed elevated adhesion and activation-associated molecules, including LFA-1, ICOS, PD-1, CD44, and CD103 compared with T-bet- Tregs, and were enriched for CD103 cells across the inflammatory time course. Adoptive transfer studies further showed that pre-existing T-bet expression enhanced recovery of antigen-specific Tregs from CFA-draining lymph nodes in a context-dependent manner, whereas T-bet expression did not confer a unique advantage in canonical in vitro suppression of Th1 proliferation. Together, these findings identify T-bet Tregs as a contact-capable regulatory subset embedded within early Th1-DC networks during the priming phase of type 1 inflammation rather than a destabilized or effector-converted Treg population.
ER -