@article{CyranSerflingKirschneretal.2022,
  author    = {Cyran, Laura and Serfling, Julia and Kirschner, Luisa and Raifer, Hartmann and Lohoff, Michael and Hermanns, Heike M. and Kerstan, Andreas and Bodem, Jochen and Lutz, Manfred B.},
  title     = {Flt3L, LIF, and IL-10 combination promotes the selective in vitro development of ESAM\(^{low}\) cDC2B from murine bone marrow},
  series = {European Journal of Immunology},
  volume    = {52},
  journal   = {European Journal of Immunology},
  number    = {12},
  doi       = {10.1002/eji.202149663},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312448},
  pages     = {1946 -- 1960},
  year      = {2022},
  abstract  = {The development of two conventional dendritic cells (DC) subsets (cDC1 and cDC2) and the plasmacytoid DC (pDC) in vivo and in cultures of bone marrow (BM) cells is mediated by the growth factor Flt3L. However, little is known about the factors that direct the development of the individual DC subsets. Here, we describe the selective in vitro generation of murine ESAM\(^{low}\) CD103\(^{-}\) XCR1\(^{-}\) CD172a\(^{+}\) CD11b\(^{+}\) cDC2 from BM by treatment with a combination of Flt3L, LIF, and IL-10 (collectively named as FL10). FL10 promotes common dendritic cell progenitors (CDP) proliferation in the cultures, similar to Flt3L and CDP sorted and cultured in FL10 generate exclusively cDC2. These cDC2 express the transcription factors Irf4, Klf4, and Notch2, and their growth is reduced using BM from Irf4\(^{-/-}\) mice, but the expression of Batf3 and Tcf4 is low. Functionally they respond to TLR3, TLR4, and TLR9 signals by upregulation of the surface maturation markers MHC II, CD80, CD86, and CD40, while they poorly secrete proinflammatory cytokines. Peptide presentation to TCR transgenic OT-II cells induced proliferation and IFN-γ production that was similar to GM-CSF-generated BM-DC and higher than Flt3L-generated DC. Together, our data support that FL10 culture of BM cells selectively promotes CDP-derived ESAM\(^{low}\) cDC2 (cDC2B) development and survival in vitro.},
  language  = {en}
}
@article{ThomannSchneiderCyranetal.2021,
  author    = {Thomann, Anna Sophie and Schneider, Theresa and Cyran, Laura and Eckert, Ina Nathalie and Kerstan, Andreas and Lutz, Manfred B.},
  title     = {Conversion of Anergic T Cells Into Foxp3\(^-\) IL-10\(^+\) Regulatory T Cells by a Second Antigen Stimulus In Vivo},
  series = {Frontiers in Immunology},
  volume    = {12},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2021.704578},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241429},
  year      = {2021},
  abstract  = {T cell anergy is a common mechanism of T cell tolerance. However, although anergic T cells are retained for longer time periods in their hosts, they remain functionally passive. Here, we describe the induction of anergic CD4\(^+\) T cells in vivo by intravenous application of high doses of antigen and their subsequent conversion into suppressive Foxp3\(^-\) IL-10\(^+\) Tr1 cells but not Foxp3\(^+\) Tregs. We describe the kinetics of up-regulation of several memory-, anergy- and suppression-related markers such as CD44, CD73, FR4, CD25, CD28, PD-1, Egr-2, Foxp3 and CTLA-4 in this process. The conversion into suppressive Tr1 cells correlates with the transient intracellular CTLA-4 expression and required the restimulation of anergic cells in a short-term time window. Restimulation after longer time periods, when CTLA-4 is down-regulated again retains the anergic state but does not lead to the induction of suppressor function. Our data require further functional investigations but at this stage may suggest a role for anergic T cells as a circulating pool of passive cells that may be re-activated into Tr1 cells upon short-term restimulation with high and systemic doses of antigen. It is tentative to speculate that such a scenario may represent cases of allergen responses in non-allergic individuals.},
  language  = {en}
}