Journal
PLOS ONE
Volume 14, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0216893
Keywords
-
Categories
Funding
- National Institutes of Health [T32-AI089474, R01-GM082916, R01-GM115234, F32-AI114109, T32-AI007024]
- American Asthma Foundation [10-0187]
- Hartwell Foundation
Ask authors/readers for more resources
CD4(+) effector/memory T cells (Tem) represent a leading edge of the adaptive immune system responsible for protecting the body from infection, cancer, and other damaging processes. However, a subset of Tem cells with low expression of CD45Rb (Rb(Lo)Tem) has been shown to suppress inflammation despite their effector surface phenotype and the lack of FoxP3 expression, the canonical transcription factor found in most regulatory T cells. In this report, we show that Rb(Lo)Tem cells can suppress inflammation by influencing Treg behavior. Co-culturing activated Rb(Lo)Tem and Tregs induced high expression of IL-10 in vitro, and conditioned media from Rb(Lo)Tem cells induced IL-10 expression in FoxP3(+) Tregs in vitro and in vivo, indicating that Rb(Lo)Tem cells communicate with Tregs in a cell-contact independent fashion. Transcriptomic and multi-analyte Luminex data identified both IL-2 and IL-4 as potential mediators of Rb(Lo)Tem-Treg communication, and antibody-mediated neutralization of either IL-4 or CD124 (IL-4Ra) prevented IL-10 induction in Tregs. Moreover, isolated Tregs cultured with recombinant IL-2 and IL-4 strongly induced IL-10 production. Using house dust mite (HDM)-induced airway inflammation as a model, we confirmed that the in vivo suppressive activity of Rb(Lo)Tem cells was lost in IL-4-ablated Rb(Lo)Tem cells. These data support a model in which Rb(Lo)Tem cells communicate with Tregs using a combination of IL-2 and IL-4 to induce robust expression of IL-10 and suppression of inflammation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available