Graphical Abstract Highlights d We identify the murine homolog of human AXL + DCs, now called transitional DCs (tDCs) d tDC development depends on Tcf4, similar to pDCs d tDCs are inefficient at IFN-I production but can efficiently activate T cells d During influenza infection, tDCs and pDCs accumulate in the lung
Phenotypic and transcriptional profiling of Treg cells at homeostasis
reveals that TCR activation promotes Treg cells with an effector phenotype
(eTreg) characterized by the production of IL-10 and expression of the
inhibitory receptor PD-1. At homeostasis, blockade of the PD-1 pathway results
in enhanced eTreg cell activity while during infection with
T.
gondii
early IFN-γ upregulates myeloid cell expression of
PD-L1 associated with reduced Treg cell populations. In infected mice, the
blockade of PD-L1, complete deletion of PD-1, or lineage-specific deletion of
PD-1 in Treg cells prevents loss of eTreg cells. These interventions resulted in
a reduced ratio of pathogen-specific effector T cells : eTregs and increased
levels of IL-10 that mitigated the development of immunopathology, but which
could compromise parasite control. Thus, eTreg cell expression of PD-1 acts as a
sensor to rapidly tune the pool of eTreg cells at homeostasis and during
inflammatory processes.
At homeostasis, a substantial proportion of Foxp3+ T regulatory cells (Tregs) have an activated phenotype associated with enhanced TCR signals and these effector Treg cells (eTregs) co-express elevated levels of PD-1 and CTLA-4. Short term in vivo blockade of the PD-1 or CTLA-4 pathways results in increased eTreg populations, while combination blockade of both pathways had an additive effect. Mechanistically, combination blockade resulted in a reduction of suppressive phospho-SHP2 Y580 in eTreg cells which was associated with increased proliferation, enhanced production of IL-10, and reduced dendritic cell and macrophage expression of CD80 and MHC-II. Thus, at homeostasis, PD-1 and CTLA-4 function additively to regulate eTreg function and the ability to target these pathways in Treg cells may be useful to modulate inflammation.
At homeostasis, a substantial proportion of Foxp3+ T regulatory cells (Tregs) have an activated phenotype associated with enhanced TCR signals and these effector Treg cells (eTregs) co-express elevated levels of PD-1 and CTLA-4. Short term in vivo blockade of the PD-1 or CTLA-4 pathways results in increased eTreg populations, while combination blockade of both pathways had an additive effect. Mechanistically, combination blockade resulted in a reduction of suppressive phospho-SHP2 Y580 in Treg cells which was associated with increased eTreg proliferation, enhanced production of IL-10, and altered dendritic cell expression of CD80 and MHC-II. Thus, at homeostasis, PD-1 and CTLA-4 function additively to regulate eTreg function and the ability to target these pathways in Treg cells may be useful to modulate inflammation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.