IL-2 can signal via chemokine receptors to promote regulatory T cells' suppressive function.
Cell Rep
; 42(8): 112996, 2023 08 29.
Article
em En
| MEDLINE
| ID: mdl-37598341
ABSTRACT
Canonical interleukin-2 (IL-2) signaling via the high-affinity CD25-containing IL-2 receptor-Janus kinase (JAK)1,3-signal transducer and activator of transcription 5 (STAT5) pathway is essential for development and maintenance of CD4+CD25HiFoxp3+ regulatory T cells (Tregs) that support immune homeostasis. Here, we report that IL-2 signaling via an alternative CD25-chemokine receptor pathway promotes the suppressive function of Tregs. Using an antibody against CD25 that biases IL-2 signaling toward this alternative pathway, we establish that this pathway increases the suppressive activity of Tregs and ameliorates murine experimental autoimmune encephalomyelitis (EAE). Furthermore, heparan sulfate, an IL-2-binding element of cell surfaces and extracellular matrix, or an engineered IL-2 immunocytokine can also direct IL-2 signaling toward this alternative pathway. Overall, these data reveal a non-canonical mechanism for IL-2 signaling that promotes suppressive functions of Tregs, further elucidates how IL-2 supports immune homeostasis, and suggests approaches to promote or suppress Treg functions.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
/
Encefalomielite Autoimune Experimental
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article