Švajger, Urban ; Obermajer, Nataša ; Jeras, Matjaž
Lately, there is increasing evidence that emphasizes the regulatory functions of IFN-Ž, which serve as negative-feedback mechanisms after, e.g., pathogen clearance, to prevent unnecessary tissue ...destruction. Inflammatory processes involving Th1 and cytotoxic responses are characterized by high, local IFN-Ž concentrations, followed by resolution and immune silencing. Although this is a well-known course of events, extensive attempts to address potential differential effects of IFN-Ž in the manner of its availability (quantitatively) in the environment do not exist. We demonstrate that high doses of IFN-Ž do not induce DC maturation and activation but instead, induce specific regulatory characteristics in DCs. Considering their phenotype, high doses of IFN-Ž extensively induce the expression of ILT-4 and HLA-G inhibitorymolecules. Interestingly, the well-known priming effect of IFN-Ž forIL-12p70 production is lost at these conditions, and the DC cytokine profile is switched toward an increased IL-10/IL-12p70 ratio upon subsequent stimulation with CD40L. Furthermore, such DCs are capable of silencing cellular immune responses and activation of cytotoxic CD8+ T lymphocytes, resulting in reduced cell proliferation and down-regulation of granzyme B expression. Additionally, we find that in this manner, immune regulation mediated by IFN-Ž is not mainly a result of increased enzymatic activity of IDO in DCs but rather, a result of HLA-G signaling, which can be reversed by blocking mAb. Altogether, our results identify a novel mechanism by which a Th1-like environment programs the functional status of DCs to silence ongoing cytotoxic responses to prevent unwanted tissue destruction and inflammation.
It was not necessary to add the material to the shelf.
Bibliographic material was successfully added on shelf.
Adding bibliographical material on shelf was not successful.
Material is already on the shelf.
Permalink
URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year
Impact factor
Edition
Category
Classification
JCR
SNIP
JCR
SNIP
JCR
SNIP
JCR
SNIP
Impact factor
Select the library membership card:
DRS,
in which the journal is indexed
Database name
Field
Year
Links to authors' personal bibliographies
Links to information on researchers in the SICRIS system
Subject headings in COBISS General List of Subject Headings
Select pickup location
The material from the parent unit is free. If the material is delivered to the pickup location from another unit, the library may charge you for this service.
