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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Human NK cells prime inflammatory DC precursors to induce Tc17 differentiation

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Author(s):
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Clavijo-Salomon, Maria A. [1, 2, 3, 4] ; Salcedo, Rosalba [1, 2] ; Roy, Soumen [1, 2] ; das Neves, Rodrigo X. [1, 2] ; Dzutsev, Amiran [1, 2] ; Sales-Campos, Helioswilton [1, 2] ; Borbely, Karen Steponavicius-Cruz [3, 5, 6] ; Silla, Lucia [7] ; Orange, Jordan S. [8] ; Mace, Emily M. [8] ; Barbuto, Jose A. M. [3, 9] ; Trinchieri, Giorgio [1, 2]
Total Authors: 12
Affiliation:
[1] NCI, Lab Integrat Canc Immunol, Ctr Canc Res, NIH, Bethesda, MD 20892 - USA
[2] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 - USA
[3] Univ Sao Paulo, Dept Immunol, Lab Tumor Immunol, Inst Biomed Sci, Med Sch, Sao Paulo - Brazil
[4] Univ Sao Paulo, Ctr Translat Res Oncol, Med Sch, Inst Canc Sao Paulo ICESP, Sao Paulo - Brazil
[5] Univ Fed Alagoas, Nutr Fac, Maceio, Alagoas - Brazil
[6] Univ Fed Alagoas, Inst Hlth & Biol Sci, Cell Biol Lab, Maceio, Alagoas - Brazil
[7] Hosp Clin Porto Alegre, Cellular Technol & Therapy Ctr, Porto Alegre, RS - Brazil
[8] Columbia Univ, Dept Pediat, Irving Med Ctr, New York, NY - USA
[9] Univ Sao Paulo, Cell & Mol Therapy Ctr NETCEM, Sao Paulo - Brazil
Total Affiliations: 9
Document type: Journal article
Source: BLOOD ADVANCES; v. 4, n. 16, p. 3990-4006, AUG 25 2020.
Web of Science Citations: 0
Abstract

Adaptive immune responses are acknowledged to evolve from innate immunity. However, limited information exists regarding whether encounters between innate cells direct the generation of specialized T-cell subsets. We aim to understand how natural killer (NK) cells modulate cell-mediated immunity in humans. We found that human CD14(+)CD16(-) monocytes that differentiate into inflammatory dendritic cells (DCs) are shaped at the early stages of differentiation by cell-to-cell interactions with NK cells. Although a fraction of monocytes is eliminated by NK-cell-mediated cytotoxicity, the polarization of interferon-gamma (IFN-gamma) at the NKp30-stabilized synapses triggers a stable IFN-gamma signature in surviving monocytes that persists after their differentiation into DCs. Notably, NK-cell-instructed DCs drive the priming of type 17 CD8(+) T cells (Tc17) with the capacity to produce IFN-gamma and interleukin-17A. Compared with healthy donors, this cellular network is impaired in patients with classical NK-cell deficiency driven by mutations in the GATA2 gene. Our findings reveal a previously unrecognized connection by which Tc17-mediated immunity might be regulated by NK-cell-mediated tuning of antigen-presenting cells. (AU)

FAPESP's process: 17/13686-9 - Rational design of a STING agonist as a model for the implementation of a platform for the development of new immunotherapies against cancer
Grantee:Maria Alejandra Clavijo Salomón
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 14/10290-9 - Modulation of natural killer cells on the differentiation and function of dendritic cells: study of the mechanisms involved and implications in cancer
Grantee:Maria Alejandra Clavijo Salomón
Support type: Scholarships abroad - Research Internship - Doctorate (Direct)
FAPESP's process: 09/54599-5 - Dendritic cells: integrative elements of the immune system - an applied approach
Grantee:Jose Alexandre Marzagão Barbuto
Support type: Research Projects - Thematic Grants
FAPESP's process: 11/05331-0 - Study of the effect of natural killer cells on the in vitro differentiation of monocytes into dendritic cells in cancer patients
Grantee:Maria Alejandra Clavijo Salomón
Support type: Scholarships in Brazil - Master
FAPESP's process: 12/23478-0 - Effect of Natural Killer cells on the in vitro differentiation of monocytes into dendritic cells in cancer patients: study of the mechanisms involved
Grantee:Maria Alejandra Clavijo Salomón
Support type: Scholarships in Brazil - Doctorate (Direct)