Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells
Dorothy K Sojka,
Beatrice Plougastel-Douglas,
Liping Yang,
Melissa A Pak-Wittel,
Maxim N Artyomov,
Yulia Ivanova,
Chao Zhong,
Julie M Chase,
Paul B Rothman,
Jenny Yu,
Joan K Riley,
Jinfang Zhu,
Zhigang Tian,
Wayne M Yokoyama
Affiliations
Dorothy K Sojka
Rheumatology Division, Washington University School of Medicine, St. Louis, United States
Beatrice Plougastel-Douglas
Rheumatology Division, Washington University School of Medicine, St. Louis, United States
Liping Yang
Rheumatology Division, Washington University School of Medicine, St. Louis, United States
Melissa A Pak-Wittel
Rheumatology Division, Washington University School of Medicine, St. Louis, United States
Maxim N Artyomov
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States
Yulia Ivanova
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States
Chao Zhong
Molecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
Julie M Chase
Rheumatology Division, Washington University School of Medicine, St. Louis, United States
Paul B Rothman
The Johns Hopkins University School of Medicine, Baltimore, United States
Jenny Yu
Rheumatology Division, Washington University School of Medicine, St. Louis, United States
Joan K Riley
Obstetrics and Gynecology Division, Washington University School of Medicine, St. Louis, United States
Jinfang Zhu
Molecular and Cellular Immunoregulation Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
Zhigang Tian
Department of Immunology, School of Life Sciences, University of Science and Technology China, Hefei, China; Hefei National Laboratory for Physical Sciences at the Microscale, Hefei, China
Wayne M Yokoyama
Rheumatology Division, Washington University School of Medicine, St. Louis, United States; Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, United States
Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells.
