| Autor: |
Lyssia Belarif, Bernard Vanhove, Nicolas Poirier |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
|
| Zdroj: |
Cell Stress, Vol 2, Iss 12, Pp 362-364 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
2523-0204 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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