GPR15⁺ T cells are Th17 like, increased in smokers and associated with multiple sclerosis

Area of Science:

• Immunology
• Neuroimmunology
• Molecular Biology

Background:

• Smoking is a known risk factor for multiple sclerosis (MS) development and progression.
• The precise mechanisms by which smoking influences MS pathogenesis remain incompletely understood.
• G protein-coupled receptor 15 (GPR15) is a molecule associated with smoking.

Purpose of the Study:

• To investigate the role of the chemokine receptor-like molecule GPR15 in the context of relapsing-remitting multiple sclerosis (RRMS).
• To explore the link between smoking, GPR15 expression, and pathogenic immune responses in RRMS.

Main Methods:

• Microarray analysis and quantitative PCR (qPCR) to assess GPR15 expression.
• Flow cytometry to quantify GPR15-expressing immune cells (T and B cells).
• In vitro cell culture with autoantigens (MBP, MOG) and analysis of cytokine production (IL-17) and cell phenotypes in cerebrospinal fluid (CSF).

Main Results:

• Elevated GPR15 expression was found in blood cells of smokers and in RRMS patients.
• Increased frequencies of GPR15-expressing T and B cells were observed in smokers.
• MBP-reactive, non-proliferating GPR15+CD4+ T cells and IL-17 production were increased in RRMS patients after antigen stimulation.
• GPR15+ T cells in the CSF of RRMS patients showed specific phenotypes and correlated with disease severity markers.

Conclusions:

• A specific proinflammatory GPR15-expressing CD4+ T cell population is identified in RRMS.
• This cell type links smoking-associated immune alterations to pathogenic mechanisms in RRMS.
• GPR15 and its ligand GPR15L may represent novel therapeutic targets in MS.