RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells

被引:0
作者
Narasimhan, Hamsa [1 ,2 ]
Richter, Maria L. [3 ]
Shakiba, Ramin [1 ,2 ]
Papaioannou, Nikos E. [2 ,22 ]
Stehle, Christina [4 ,5 ,6 ]
Rengarajan, Kaushikk Ravi [1 ]
Ulmert, Isabel [7 ]
Kendirli, Arek [8 ,9 ,10 ]
de la Rosa, Clara [8 ,9 ,11 ]
Kuo, Pin-Yu [1 ,2 ]
Altman, Abigail [12 ,13 ]
Muench, Philipp [14 ,15 ]
Mahboubi, Saba [14 ,15 ]
Kuentzel, Vanessa [2 ]
Sayed, Amina [1 ]
Stange, Eva-Lena [16 ]
Pes, Jonas [16 ]
Antonova, Alina Ulezko [17 ]
Pereira, Carlos-Filipe [12 ,13 ]
Klein, Ludger [1 ]
Dudziak, Diana [18 ]
Colonna, Marco [17 ]
Torow, Natalia [16 ,23 ]
Hornef, Mathias W. [16 ]
Clausen, Bjoern E. [14 ]
Kerschensteiner, Martin [8 ,9 ,10 ]
Lahl, Katharina [7 ,19 ,20 ,21 ]
Romagnani, Chiara
Colome-Tatche, Maria [3 ]
Schraml, Barbara U. [1 ,2 ]
机构
[1] Ludwig Maximilians Univ Munchen, Biomed Ctr Munich BMC, Fac Med, D-82152 Planegg Martinsried, Germany
[2] Ludwig Maximilians Univ Munchen, Fac Med, Biomed Ctr, Inst Cardiovasc Physiol & Pathophysiol, D-82152 Planegg Martinsried, Germany
[3] Ludwig Maximilians Univ Munchen, Biomed Ctr Munich Physiol Chem, D-82152 Planegg Martinsried, Germany
[4] Charite Univ med Berlin, Inst Med Immunol, Berlin, Germany
[5] Free Univ Berlin, D-10117 Berlin, Germany
[6] Humboldt Univ, D-10117 Berlin, Germany
[7] Tech Univ Denmark, DTU Danchip, DK-2800 Lyngby, Denmark
[8] Ludwig Maximilians Univ Munchen, Inst Clin Neuroimmunol Univ Hosp, Planegg Martinsried, Germany
[9] Ludwig Maximilians Univ Munchen, Med Fac, Biomed Ctr, D-82152 Planegg Martinsried, Germany
[10] Munich Cluster Syst Neurol SyNergy, Munich, Germany
[11] LMU, Grad Sch Syst Neurosci, D-82152 Planegg Martinsried, Germany
[12] Lund Univ, Lund Stem Cell Ctr, Mol Med & Gene Therapy, Lund, Sweden
[13] Wallenberg Ctr Mol Med, Lund, Sweden
[14] Johannes Gutenberg Univ Mainz, Univ Med Ctr Johannes Gutenberg, Inst Mol Med, D-55131 Mainz, Germany
[15] Johannes Gutenberg Univ Mainz, Univ Med Ctr Johannes Gutenberg, Res Ctr Immunotherapy, D-55131 Mainz, Germany
[16] Rhein Westfal TH Aachen, Univ Hosp, D-52074 Aachen, Germany
[17] Washington Univ Sch Med, Dept Pathol & Immunol, Dept Pathol & Immunol, St Louis, MO 63110 USA
[18] Friedrich Schiller Univ, Jena Univ Hosp, Inst Immunol, D-07743 Jena, Germany
[19] Immunol Sect, S-22184 Lund, Sweden
[20] Univ Calgary, Calvin Phoebe & Joan Snyder Inst Chron Dis, Calgary, AB T2N 1N4, Canada
[21] Univ Calgary, Cumming Sch Med, Dept Microbiol Immunol & Infect Dis, Calgary, AB T2N 1N4, Canada
[22] Biomed Res Fdn Acad Athens, Ctr Basic Res, Immune Regulat Lab, Athens 11527, Greece
[23] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany
关键词
dendritic cells; ROR gamma t; AIRE; innate lymphocytes; antigen presenting cells; INNATE LYMPHOID-CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FLT3; LIGAND; IMMUNITY; RECEPTOR; PRDM16; ACTIVATION; SELECTION;
D O I
暂无
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Conventional dendritic cells (cDCs) are potent antigen- presenting cells (APCs) that integrate signals from their environment allowing them to direct situation- adapted immunity. Thereby they harbor great potential for being targeted in vaccination, autoimmunity, and cancer. Here, we use fate mapping, functional analyses, and comparative cross- species transcriptomics to show that ROR gamma t+DCs are a conserved, functionally versatile, and transcriptionally distinct type of DCs. ROR gamma t+ DCs entail various populations described in different contexts including Janus cells/ROR gamma t- expressing extrathymic Aire- expressing cells (eTACs), subtypes of Thetis cells, ROR gamma t+-DC (R- DC) like cells, cDC2C and ACY3+ DCs. We show that in response to inflammatory triggers, ROR gamma t+ DCs can migrate to lymph nodes and in the spleen can activate na & iuml;ve CD4+ T cells. These findings expand the functional repertoire of ROR gamma t+ DCs beyond the known role of eTACs and Thetis cells in inducing T cell tolerance to self- antigens and intestinal microbes in mice. We further show that ROR gamma t+ DCs with proinflammatory features accumulate in autoimmune neuroinflammation in mice and men. Thus, our work establishes ROR gamma t+ DCs as immune sentinel cells that exhibit a broad functional spectrum ranging from inducing peripheral T cell tolerance to T cell activation depending on signals they integrate from their environment.
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页数:12
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