Abstract
During chronic inflammatory disorders, a persistent natural killer (NK) cell derangement is observed. While increased cell turnover is expected, little is known about whether and how NK-cell homeostatic balance is maintained. Here, flow cytometric analysis of peripheral blood mononuclear cells in chronic inflammatory disorders, both infectious and non-infectious, reveals the presence of a CD34(+)CD226(DNAM-1)(bright)CXCR4(+) cell population displaying transcriptional signatures typical of common lymphocyte precursors and giving rise to NK-cell progenies with high expression of activating receptors and mature function and even to α/β T lymphocytes. CD34(+)CD226(bright)CXCR4(+) cells reside in bone marrow, hardly circulate in healthy donors and are absent in cord blood. Their proportion correlates with the degree of inflammation, reflecting lymphoid cell turnover/reconstitution during chronic inflammation. These findings provide insight on intermediate stages of NK-cell development, a view of emergency recruitment of cell precursors, and upgrade our understanding and monitoring of chronic inflammatory conditions.
Publication types
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Multicenter Study
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Observational Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD34 / metabolism
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Bone Marrow / immunology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology*
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Bone Marrow Cells / metabolism
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Case-Control Studies
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Fetal Blood / cytology
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Flow Cytometry
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Fluorescent Antibody Technique
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Gene Expression Profiling
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HIV Infections / genetics
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HIV Infections / immunology*
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Hepatitis C, Chronic / genetics
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Hepatitis C, Chronic / immunology*
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Humans
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Killer Cells, Natural / cytology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / immunology*
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Leukocytes, Mononuclear / metabolism
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Lymphoid Progenitor Cells / cytology
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Lymphoid Progenitor Cells / immunology*
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Lymphoid Progenitor Cells / metabolism
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Pulmonary Disease, Chronic Obstructive / genetics
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Pulmonary Disease, Chronic Obstructive / immunology*
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Receptors, CXCR4 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Tuberculosis, Pulmonary / genetics
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Tuberculosis, Pulmonary / immunology*
Substances
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Antigens, CD34
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Antigens, Differentiation, T-Lymphocyte
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CD226 antigen
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CXCR4 protein, human
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Receptors, CXCR4