Human Fc Receptor-like 3 Inhibits Regulatory T Cell Function and Binds Secretory IgA.
Cell Rep
; 30(5): 1292-1299.e3, 2020 02 04.
Article
em En
| MEDLINE
| ID: mdl-32023449
ABSTRACT
Human Fc receptor-like 3 (FCRL3) is an orphan receptor expressed by lymphocytes, including regulatory T cells. FCRL3 is implicated in several autoimmune diseases; however, its function on regulatory T cells is unknown. We discovered that FCRL3 stimulation of regulatory T cells inhibited their suppressive function. Moreover, FCRL3 stimulation induced IL-17, IL-26, and IFNγ production and promoted expression of the Th17-defining transcription factor RORγt without affecting FOXP3 expression. We suggest that FCRL3 engagement mediates a transition of regulatory T cells to a pro-inflammatory Th17-like phenotype. In addition, we identified secretory IgA as a specific FCRL3 ligand. Secretory IgA could serve as an environmental cue for mucosal breaches and locally drive regulatory T cell plasticity to help control infection. Our findings define a mechanism that explains the recognized association of FCRL3 with autoimmune diseases. Targeting FCRL3 to modulate regulatory T cell activity could be exploited to treat both malignancies and autoimmune diseases.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina A Secretora
/
Receptores Imunológicos
/
Linfócitos T Reguladores
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos