Full antagonist of the IL-7 receptor suppresses chronic inflammation in non-human primate models by controlling antigen-specific memory T cells
Authors:Lyssia Belarif1, Bernard Vanhove1 and Nicolas Poirier1
1 OSE Immunotherapeutics, Nantes, France.
Keywords:
Chronic inflammation, IL-7, IL-7 receptor, memory T cells, monoclonal antibody.
Corresponding Author(s):
Conflict of interest statement:
The authors of this manuscript have conflicts of interest to disclose: BV and NP are shareholders of OSE Immunotherapeutics, a company owning IL-7 receptor antagonists.
Please cite this article as:
Lyssia Belarif, Bernard Vanhove and Nicolas Poirier (2018). Full antagonist of the IL-7 receptor suppresses chronic inflammation in non-human primate models by controlling antigen-specific memory T cells. Cell Stress 2(12): 362-364. doi: 10.15698/cst2018.12.168
© 2018 Belarif et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Targeting the expansion of pathogenic memory immune cells is a promising therapeutic strategy to prevent chronic autoimmune attacks. Interleukin 7 (IL-7) is a limiting and potent cytokine produced by epithelial and stromal cells sustaining T-lymphocytes development, homeostasis and cell metabolism. Almost all conventional mature T lymphocytes express the IL-7 receptor (IL-7R), with the exception for naturally-occurring regulatory T-cells (Treg), constituting a rare opportunity to selectively strangle pathogenic effectors while preserving crucial natural regulators. In our recent study, we reported that therapeutic efficacy of antagonist anti- IL-7Rα mAbs in a non-human primate model of memory T cell-induced chronic inflammation depends on recognition of an epitope overlapping the IL-7 binding domain (site 1) and the receptor heterodimerization region (site-2b) (Nat Commun, 9(1):4483). We found that “site-1-only” mAbs prevented IL-7-induced JAK/STAT signaling but induced PI3K and Erk signaling and lacked efficacy in vivo, whereas “site-1 + 2b” mAbs were fully antagonist and demonstrated potent activity to control skin inflammation on the long term. The mechanism of action comprised the neutralization of IFN-γ producing antigen-specific memory T cells, without inducing lymphopenia or polyclonal T-cell functional or metabolic defects as generally observed previously in rodents.