VSIG-3 as a ligand of VISTA inhibits human T-cell function.
Antibodies, Neutralizing
/ pharmacology
B7 Antigens
/ agonists
Cell Adhesion Molecules
/ agonists
Cell Proliferation
Cells, Cultured
Cytokines
/ metabolism
Humans
Immune Tolerance
Immunoglobulins
/ genetics
Immunotherapy
/ trends
Ligands
Lymphocyte Activation
RNA, Small Interfering
/ genetics
Receptors, Antigen, T-Cell
/ metabolism
Signal Transduction
T-Lymphocytes
/ immunology
B7 family
VISTA/PD-1H
VSIG-3/IGSF11
immune checkpoints
immunotherapy
Journal
Immunology
ISSN: 1365-2567
Titre abrégé: Immunology
Pays: England
ID NLM: 0374672
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
19
01
2018
revised:
27
08
2018
accepted:
31
08
2018
pubmed:
17
9
2018
medline:
10
7
2019
entrez:
17
9
2018
Statut:
ppublish
Résumé
B7 family members and their receptors play a central role in the regulation of T-cell responses through T-cell co-stimulation and co-inhibition pathways that constitute attractive targets for the development of immunotherapeutic drugs. In this study, we report that VSIG-3/IGSF11 is a ligand of B7 family member VISTA/PD-1H and inhibits human T-cell functions through a novel VSIG-3/VISTA pathway. An extensive functional ELISA binding screening assay reveals that VSIG-3 binds to the new B7 family member VISTA but does not interact with other known members of the B7 family. Under the same experimental conditions, we did not observe any significant interaction between VSIG-8 and VISTA. In addition, VSIG-3 inhibits human T-cell proliferation in the presence of T-cell receptor signaling. Furthermore, VSIG-3 significantly reduces cytokine and chemokine production by human T cells including IFN-γ, IL-2, IL-17, CCL5/Rantes, CCL3/MIP-1α, and CXCL11/I-TAC. Anti-VISTA neutralization antibodies attenuate the binding of VSIG-3 and VISTA, as well as VSIG-3-induced T-cell inhibition. Hence, we have identified a novel ligand for VISTA that is able to inhibit human T-cell proliferation and cytokine production. This unique VSIG-3/VISTA co-inhibitory pathway may provide new strategies for the treatment of human cancers, autoimmune disorders, infection, and transplant rejection and may aid in the design of better vaccines.
Identifiants
pubmed: 30220083
doi: 10.1111/imm.13001
pmc: PMC6283650
doi:
Substances chimiques
Antibodies, Neutralizing
0
B7 Antigens
0
Cell Adhesion Molecules
0
Cytokines
0
IGSF11 protein, human
0
Immunoglobulins
0
Ligands
0
RNA, Small Interfering
0
Receptors, Antigen, T-Cell
0
VSIR protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
74-85Informations de copyright
© 2018 John Wiley & Sons Ltd.
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