% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Kurt:182685,
      author       = {A. S. Kurt and K. Strobl and P. Ruiz and G. Osborn and T.
                      Chester and L. Dawson and K. M. Warwas$^*$ and E. H. Grey
                      and S. Mastoridis and E. Kodela and N. Safinia and A.
                      Sanchez-Fueyo and M. Martinez-Llordella},
      title        = {{IL}-2 availability regulates the tissue specific phenotype
                      of murine intra-hepatic {T}regs.},
      journal      = {Frontiers in immunology},
      volume       = {13},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2022-02853},
      pages        = {1040031},
      year         = {2022},
      abstract     = {CD4+CD25+Foxp3+ Tregs are known to acquire tissue-specific
                      features and exert cytoprotective and regenerative
                      functions. The extent to which this applies to
                      liver-resident Tregs is unknown. In this study, we aimed to
                      explore the phenotypic and functional characteristics of
                      adult murine liver resident Tregs during homeostasis.
                      Additionally, we investigated their role in ameliorating
                      liver inflammation and tissue damage. Quantification of
                      Foxp3+CD4+CD25+ cells comparing different tissues showed
                      that the liver contained significantly fewer resident Tregs.
                      A combination of flow cytometry phenotyping and microarray
                      analysis of intra-hepatic and splenic Tregs under
                      homeostatic conditions revealed that, although intra-hepatic
                      Tregs exhibited the core transcriptional Treg signature,
                      they expressed a distinct transcriptional profile. This was
                      characterized by reduced CD25 expression and increased
                      levels of pro-inflammatory Th1 transcripts Il1b and Ifng. In
                      vivo ablation of Tregs in the Foxp3-DTR mouse model showed
                      that Tregs had a role in reducing the magnitude of systemic
                      and intra-hepatic inflammatory responses following acute
                      carbon tetrachloride (CCl₄) injury, but their absence did
                      not impact the development of hepatocyte necrosis.
                      Conversely, the specific expansion of Tregs by
                      administration of IL-2 complexes increased the number of
                      intra-hepatic Tregs and significantly ameliorated tissue
                      damage following CCl₄ administration in C57BL/6 mice. The
                      cytoprotective effect observed in response to IL-2c was
                      associated with the increased expression of markers known to
                      regulate Treg suppressive function. Our results offer
                      insight into the transcriptome and complex immune network of
                      intra-hepatic Tregs and suggest that strategies capable of
                      selectively increasing the pool of intra-hepatic Tregs could
                      constitute effective therapies in inflammatory liver
                      diseases.},
      keywords     = {CCl₄ induced liver injury (Other) / Treg depletion
                      (Other) / acute inflammation (Other) / liver (Other) /
                      regulatory T cells (Tregs) (Other) / tissue specific
                      (Other)},
      cin          = {D121},
      ddc          = {610},
      cid          = {I:(DE-He78)D121-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36389734},
      pmc          = {pmc:PMC9661520},
      doi          = {10.3389/fimmu.2022.1040031},
      url          = {https://inrepo02.dkfz.de/record/182685},
}