IL10- and IL35-Secreting MutuDC Lines Act in Cooperation to Inhibit Memory T Cell Activation Through LAG-3 Expression

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State: Public
Version: author
License: CC BY 4.0
Serval ID
serval:BIB_505F034B5FD7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
IL10- and IL35-Secreting MutuDC Lines Act in Cooperation to Inhibit Memory T Cell Activation Through LAG-3 Expression
Journal
Frontiers in Immunology
Author(s)
Koga Marianna M., Engel Adrien, Pigni Matteo, Lavanchy Christine, Stevanin Mathias, Laversenne Vanessa, Schneider Bernard L., Acha-Orbea Hans
ISSN
1664-3224
ISSN-L
1664-3224
Publication state
Published
Issued date
17/02/2021
Peer-reviewed
Oui
Volume
12
Pages
607315
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Dendritic cells (DCs) are professional antigen-presenting cells involved in the initiation of immune responses. We generated a tolerogenic DC (tolDC) line that constitutively secretes interleukin-10 (IL10-DCs), expressed lower levels of co-stimulatory and MHCII molecules upon stimulation, and induced antigen-specific proliferation of T cells. Vaccination with IL10-DCs combined with another tolDC line that secretes IL-35, reduced antigen-specific local inflammation in a delayed-type hypersensitivity assay independently on regulatory T cell differentiation. In an autoimmune model of rheumatoid arthritis, vaccination with the combined tolDCs after the onset of the disease impaired disease development and promoted recovery of mice. After stable memory was established, the tolDCs promoted CD4 downregulation and induced lymphocyte activation gene 3 (LAG-3) expression in reactivated memory T cells, reducing T cell activation. Taken together, our findings indicate the benefits of combining anti-inflammatory cytokines in an antigen-specific context to treat excessive inflammation when memory is already established.
Keywords
IL-10, IL-35, LAG-3, dendritic cells, tolerogenic DCs
Pubmed
Web of science
Open Access
Yes
Funding(s)
Swiss National Science Foundation
Create date
16/03/2021 8:27
Last modification date
13/07/2021 5:36
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