Intestinal barrier tissues are colonized by myriad microbes, producing a large variety of antigens, metabolites, and small molecules. The intestines are home to different subsets of T cells responding to these signals and playing important roles in antimicrobial defense as well as maintenance of tolerance and local tissue homeostasis. Recently (Hackstein et al. Nat. Communications, 2022), it was discovered that commensal-reactive T cells can acquire a polyfunctional, innate-like phenotype (MHC II-restricted, innate-like and commensal-reactive T cells = TMIC), potentially enabling these cells to participate in a large range of inflammatory settings as well as endowing them with the potential to contribute to tissue repair.
It is currently unknown, which exact signals allow T cells to acquire this phenotype. Hence, one of the primary objectives of the group is to unravel the developmental pathways underlying the TMIC phenotype using mouse models including germ-free mice as well as TCR-transgenic animals.
Another focus of the group will be to study how the presence of TMIC cells and other microbe-reactive cells affects barrier integrity using mouse models as well as transcriptional approaches and in vitro models of wound healing and related processes.
As there is ample crosstalk between anti-microbial T cells and other local immune as well as parenchymal cells, these studies will be conducted in close collaborations with other IMI groups, allowing for a more comprehensive understanding of the impact of microbe-immune interactions.
To translate findings into the human system, it is planned to confirm key results in experiments on human intestinal T cells in collaboration with the Janssen group.
As the majority of the work will be conducted at the Campus Weihenstephan in Freising, it is also planned to work closely with the group of Dietmar Zehn to study the impact of antimicrobial immunity on wider systemic immune responses.
Hackstein CP et al. A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice. Nat Commun. 2022 Dec.
Hackstein CP, Spitzer J et al. Interferon-induced IL-10 drives systemic T-cell dysfunction during chronic liver injury. J Hepatol. 2023 Mar
Leng T, Akther HD, Hackstein CP et al. TCR and Inflammatory Signals Tune Human MAIT Cells to Exert Specific Tissue Repair and Effector Functions. Cell Rep. 2019 Sep
Hackstein CP, Assmus LM et al. Gut microbial translocation corrupts myeloid cell function to control bacterial infection during liver cirrhosis. Gut. 2017 Mar
A complete list of our publications can be found here, on Pubmed.
We are currently supported by institutional funds.