Abstract
Group 2 innate lymphoid cells (ILC-2s) regulate immune responses to pathogens and maintain tissue homeostasis in response to cytokines. Positive regulation of ILC-2s through ICOS has been recently elucidated. We demonstrate here that PD-1 is an important negative regulator of KLRG1+ ILC-2 function in both mice and humans. Increase in KLRG1+ ILC-2 cell numbers was attributed to an intrinsic defect in PD-1 signaling, which resulted in enhanced STAT5 activation. During Nippostrongylus brasiliensis infection, a significant expansion of KLRG1+ ILC-2 subsets occurred in Pdcd1-/- mice and, upon adoptive transfer, Pdcd1-/- KLRG1+ ILC-2s significantly reduced worm burden. Furthermore, blocking PD-1 with an antibody increased KLRG1+ ILC-2 cell number and reduced disease burden. Therefore, PD-1 is required for maintaining the number, and hence function, of KLRG1+ ILC-2s.
© 2017 Taylor et al.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Gene Expression Profiling
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Gene Expression Regulation
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Homeodomain Proteins / metabolism
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Humans
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Immunity, Innate*
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Lectins, C-Type / metabolism*
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Lymphocyte Count
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Lymphocyte Subsets / metabolism
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Lymphocytes / metabolism*
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Mice, Inbred C57BL
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Nippostrongylus / physiology
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Parasites / physiology
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Programmed Cell Death 1 Receptor / deficiency
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Programmed Cell Death 1 Receptor / metabolism*
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Receptors, Immunologic / metabolism*
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STAT5 Transcription Factor / metabolism
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Signal Transduction
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Strongylida Infections / immunology
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Strongylida Infections / pathology
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Trans-Activators / metabolism*
Substances
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Homeodomain Proteins
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KLRG1 protein, human
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Klrg1 protein, mouse
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Lectins, C-Type
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PDCD1 protein, human
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Pdcd1 protein, mouse
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Programmed Cell Death 1 Receptor
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Receptors, Immunologic
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STAT5 Transcription Factor
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Trans-Activators
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RAG-1 protein