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Human CCR6 + Th cells show both an extended stable gradient of Th17 activity and imprinted plasticity.
Singh, Satya P; Parween, Farhat; Edara, Nithin; Zhang, Hongwei H; Chen, Jinguo; Otaizo-Carrasquero, Francisco; Cheng, Debby; Oppenheim, Nicole A; Ransier, Amy; Zhu, Wenjun; Shamsaddini, Amirhossein; Gardina, Paul J; Darko, Samuel W; Singh, Tej Pratap; Douek, Daniel C; Myers, Timothy G; Farber, Joshua M.
Afiliación
  • Singh SP; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Parween F; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Edara N; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Zhang HH; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Chen J; Center for Human Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Otaizo-Carrasquero F; Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Cheng D; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Oppenheim NA; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Ransier A; Genome Analysis Core, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Zhu W; Retinal Neurophysiology Section, National Eye Institute, National Institutes of Health, Bethesda, MD.
  • Shamsaddini A; Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Gardina PJ; Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Darko SW; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Singh TP; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Douek DC; Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
  • Myers TG; Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
  • Farber JM; Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD.
bioRxiv ; 2023 Jan 06.
Article en En | MEDLINE | ID: mdl-36789418
Th17 cells have been investigated in mice primarily for their contributions to autoimmune diseases. However, the pathways of differentiation of Th17 and related (type 17) cells and the structure of the type 17 memory population in humans are not well understood; such understanding is critical for manipulating these cells in vivo . By exploiting differences in levels of surface CCR6, we found that human type 17 memory cells, including individual T cell clonotypes, form an elongated continuum of type 17 character along which cells can be driven by increasing RORγt. This continuum includes cells preserved within the memory pool with potentials that reflect the early preferential activation of multiple over single lineages. The CCR6 + cells' phenotypes and epigenomes are stable across cell divisions under homeostatic conditions. Nonetheless, activation in polarizing and non-polarizing conditions can yield additional functionalities, revealing, respectively, both environmentally induced and imprinted mechanisms that contribute differentially across the continuum to yield the unusual plasticity ascribed to type 17 cells.