N-terminal ectodomain of BTNL2 inhibits T cell activation via a non-canonical interaction with its putative receptor that results in a delayed progression of DSS-induced ulcerative colitis.
Mol Immunol
; 166: 39-49, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38219401
ABSTRACT
Butyrophilin-like 2 (BTNL2) is a T cell inhibitory molecule that interacts with unknown binding partners to modulate the immune response in a number of inflammatory and autoimmune diseases. In this study, we found that the inhibitory effects of BTNL2 on T cell activation and effector functions can be executed by its N-terminal IgV domain (BTNL2 IgV1) alone. Structure-guided mutation of key residues on BTNL2 IgV1 based on known receptor-ligand interfaces involving immunoglobulin superfamily members revealed that BTNL2 uses a non-canonical binding interface with its putative receptor. A high avidity BTNL2 IgV1 probe revealed that in an inducible model of ulcerative colitis, severe colitis was accompanied by a selective enrichment of BTNL2-receptor expressing effector-memory CD4+ and CD8+ T cells in the Peyer's patches. Intraperitoneal administration of BTNL2 IgV1 resulted in a significant delay in the progression of DSS-induced colitis and also showed reduced activation of the BTNL2-receptor-expressing T cells in the Peyer's patches. Thus, this study demonstrates that the BTNL2-receptor-expressing T cells in the Peyer's patches participate in the disease pathogenesis and can serve as a novel therapeutic target in ulcerative colitis, which can be modulated by BTNL2 IgV1.
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Base de dados:
MEDLINE
Assunto principal:
Colite Ulcerativa
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Colite
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article