Exacerbated experimental autoimmune encephalomyelitis in mast-cell-deficient Kit W-sh/W-sh mice

Area of Science:

• Neuroimmunology
• Autoimmune diseases
• Experimental models of Multiple Sclerosis

Background:

• Mast cells (MCs) have been implicated in multiple sclerosis (MS) pathogenesis.
• Previous studies using Kit(W/W-v) mice suggested MCs exacerbate experimental autoimmune encephalomyelitis (EAE).
• The role of MCs in EAE requires further clarification using distinct genetic models and protocols.

Purpose of the Study:

• To investigate the role of mast cells (MCs) in experimental autoimmune encephalomyelitis (EAE) using the Kit(W-sh/W-sh) mouse model.
• To compare EAE development in Kit(W-sh/W-sh) and Kit(W/W-v) mice under varying immunization conditions.
• To determine the impact of mast cell reconstitution on EAE severity.

Main Methods:

• Induction of chronic EAE in mast cell-deficient Kit(W-sh/W-sh) and control Kit(+/+) mice using MOG(35-55).
• Comparison of EAE severity, central nervous system (CNS) inflammation, and T-cell responses between different mouse strains and immunization protocols.
• Bone marrow-derived mast cell reconstitution in Kit(W-sh/W-sh) mice, both systemically and within the CNS.

Main Results:

• EAE was unexpectedly exacerbated in Kit(W-sh/W-sh) mice compared to controls, showing increased CNS inflammation and T-cell responses.
• Kit(W/W-v) mice showed protection from EAE only with high-dose immunization, unlike Kit(W-sh/W-sh) mice which showed exacerbated EAE across all protocols.
• Systemic, but not CNS-specific, mast cell reconstitution in Kit(W-sh/W-sh) mice did not prevent EAE exacerbation.

Conclusions:

• These findings challenge the previous understanding of mast cell (MC) contribution to EAE.
• The experimental model and immunization protocol significantly influence MCs' role in EAE pathogenesis.
• MCs may exert a protective role in EAE, potentially mediated within the central nervous system (CNS).