Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells.
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. DOI: http://dx.doi.org/10.7554/eLife.01659.001.
Rheumatology Division, Washington University School of Medicine, St. Louis, United States.
Dorothy K
DK
Sojka
Beatrice
B
Plougastel-Douglas
Liping
L
Yang
Melissa A
MA
Pak-Wittel
Maxim N
MN
Artyomov
Yulia
Y
Ivanova
Chao
C
Zhong
Julie M
JM
Chase
Paul B
PB
Rothman
Jenny
J
Yu
Joan K
JK
Riley
Jinfang
J
Zhu
Zhigang
Z
Tian
Wayne M
WM
Yokoyama
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019070:Cell Lineage; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics; D014599:Uterus / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D015415:Biomarkers; D014157:Transcription Factors
liver; skin; uterus