CCL22 regulates experimental autoimmune encephalomyelitis by controlling inflammatory macrophage accumulation and
Rukiye-Nazan E Dogan1, Nancy Long, Eileen Forde
1Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Journal of Leukocyte Biology
|October 14, 2010
Summary
CCL22 blockade delays experimental autoimmune encephalomyelitis (EAE) onset and reduces severity by limiting pathogenic macrophage infiltration into the central nervous system (CNS). This suggests CCL22 is a key regulator of EAE development.
Area of Science:
- Neuroimmunology
- Autoimmune Diseases
- Demyelinating Disorders
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a widely used mouse model for multiple sclerosis (MS).
- CCL22 expression is elevated during EAE development, suggesting a role in disease pathogenesis.
Purpose of the Study:
- To investigate the role of CCL22 in EAE development and progression.
- To determine if targeting CCL22 can ameliorate EAE.
Main Methods:
- Administration of anti-CCL22 antibodies during EAE induction and at disease onset.
- Assessment of clinical EAE scores, CNS pathology, and immune cell infiltration.
- Analysis of T cell responses and macrophage phenotype in vitro and in vivo.
Main Results:
- Anti-CCL22 treatment at immunization delayed EAE onset and reduced disease severity, correlating with decreased CNS pathology and macrophage infiltration.
- Treatment at disease onset did not affect disease progression.
- CCL22 neutralization shifted macrophage phenotype towards an M2-like state with reduced TNF and increased IL-10 production.
Conclusions:
- CCL22 is a critical chemokine in regulating EAE pathogenesis, primarily through the recruitment and modulation of macrophage function in the CNS.
- Targeting CCL22 may represent a therapeutic strategy for demyelinating diseases like MS, particularly when administered early in the disease process.
