The CD318/CD6 axis limits type 1 diabetes islet autoantigen-specific human T cell activation.
J Autoimmun
; 146: 103228, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38642507
ABSTRACT
CD6 is a glycoprotein expressed on CD4 and CD8 T cells involved in immunoregulation. CD318 has been identified as a CD6 ligand. The role of CD318 in T cell immunity is restricted as it has only been investigated in a few mice autoimmune models but not in human diseases. CD318 expression was thought to be limited to mesenchymal-epithelial cells and, therefore, contribute to CD6-mediated T cell activation in the CD318-expressing tissue rather than through interaction with antigen-presenting cells. Here, we report CD318 expression in a subpopulation of CD318+ myeloid dendritic (mDC), whereas the other peripheral blood populations were CD318 negative. However, CD318 can be induced by activation a subset of monocytes treated with LPS and IFNγ and in vitro monocyte derived DCs were CD318+. We also showed that recombinant CD318 inhibited T cell function. Strikingly, CD318+ DCs suppressed the proliferation of autoreactive T cells specific for GAD65, a well-known targeted self-antigen in Type 1 Diabetes (T1D). Our study provides new insight into the role of the CD318/CD6 axis in the immunopathogenesis of inflammation, suggesting a novel immunoregulatory role of CD318 in T cell-mediated autoimmune diseases and identifying a potential novel immune checkpoint inhibitor as a target for intervention in T1D which is an unmet therapeutic need.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Autoantígenos
/
Células Dendríticas
/
Activación de Linfocitos
/
Antígenos CD
/
Islotes Pancreáticos
/
Diabetes Mellitus Tipo 1
Límite:
Humans
Idioma:
En
Revista:
J Autoimmun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2024
Tipo del documento:
Article