A TLR/CD44 axis regulates T cell trafficking in experimental and human multiple sclerosis

Area of Science:

• Immunology
• Neuroimmunology
• Molecular Biology

Background:

• Leukocyte trafficking is crucial in autoimmune disorders but poorly understood.
• Toll-like receptor 2 (TLR2) ligands are implicated in modulating immune responses.

Purpose of the Study:

• To investigate the effect of TLR2 ligands on T helper cell trafficking via CD44 isoform repertoire modulation.
• To explore the role of TLR2 and CD44 in the pathogenesis of central nervous system (CNS) autoimmune diseases.

Main Methods:

• Analysis of CD44 isoform expression in T helper cells.
• Investigation of TLR2 ligand effects on immune cell trafficking.
• Examination of Wnt/β-catenin signaling and splicing factor expression.
• Study of CD44 binding to osteopontin.

Main Results:

• TLR2 ligand engagement reshuffled CD44 isoforms in T helper cells.
• Specific CD44 isoforms (mCD44 and hCD44) were enriched in the CNS during experimental autoimmune encephalomyelitis (EAE) and in cerebrospinal fluid of multiple sclerosis (MS) patients.
• CD44 variants showed increased binding to osteopontin.
• TLR engagement modulated CD44 variants in human T helper cells.

Conclusions:

• TLR2 ligands modulate T helper cell distribution in the CNS by altering CD44 isoforms.
• This mechanism is implicated in lesion distribution in CNS autoimmune diseases.
• Interference with TLR-CD44 interactions presents a potential therapeutic strategy for autoimmune relapses.