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Schlenner, S. M.

Publications and source records attributed to Schlenner, S. M..

2 recordsLinked to original sources
bioRxiv2025

The quest continues: Human CD4+ CD16+ CD56+ "exTreg" resemble NKT cells instead

Regulatory T cells are essential for immune tolerance, but their loss of function under inflammatory conditions in murine models signify a risk factor for Treg-based therapies. Recently CD4+ CD56+ CD16+ T cells were suggested to resemble such ex-Treg in human PBMC. Here, we re-evaluate the identity of the CD4+ CD56+ CD16+ population at a phenotypic and transcriptomic level using multiparametric flow cytometry on human PBMC and CITE-seq analysis to demonstrate that the CD4+ CD56+ CD16+ cells mostly constitute NKT cells instead. Further, we evaluated the stability of human Treg under lineage-challenging conditions and observe robust lineage stability in vitro. Finally, we also explore the potential of Tr17 induction using TGF-{beta} and IL-6, a possible therapeutic strategy for Treg ex vivo expansion-based therapies. Together, we conclude that human exTreg remain to be described and instead human Treg present as remarkably stable, further promoting Treg-based adoptive transfer therapies.

immunology↗
bioRxiv2023

The tissue-resident regulatory T cell pool is shaped by transient multi-tissue migration and a conserved residency program

The tissues are the site of many of the most important immunological reactions, yet the immunology of the tissues has remained relatively opaque. Recent studies have identified Foxp3+ regulatory T cells (Tregs) in several non-lymphoid tissues. These tissue-resident populations have been ascribed unique characteristics based on comparisons to lymphoid Tregs. Here we performed a systematic analysis of the Treg population residing in non-lymphoid organs throughout the body, revealing shared phenotypes, transient residency and common molecular dependencies. Further, tissue Tregs from different non-lymphoid organs shared T cell receptor (TCR) sequences, with functional capacity to drive multi-tissue Treg entry. Finally, tissue Tregs extracted from non-lymphoid organs were tissue-agnostic on re-entry, without homing preference for their tissue of origin. Together these results demonstrate that the tissue-resident Treg pool in most non-lymphoid organs, other than the gut, is largely constituted by broadly self-reactive Tregs, characterised by transient multi-tissue migration and a common residency program.

immunology↗