CCL22 regulates experimental autoimmune encephalomyelitis by controlling inflammatory macrophage accumulation and effector function

Journal of Leukocyte Biology

Nancy Long¹  Rukiye-Nazan E. Dogan¹  William J. Karpus –¹  Kristen Dennis¹  Eileen Forde¹  Stephen D. Miller – and¹  Adam P. Kohm¹ 

[1] Departments of Pathology and  Microbiology-Immunology, Interdepartmental Immunobiology Center, Center for Genetic Medicine, and –Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

关键词: trafficking;    migration;    CNS;    multiple sclerosis;    autoimmunity;    EAE;   

DOI  :  10.1189/jlb.0810442

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

EAE is a demyelinating disease of the CNS and serves as a mouse model of MS. Expression of CCL22 in the draining LNs and spinal cord correlated with the onset of clinical EAE development and remained elevated. Administration of anti-CCL22 at the time of autoantigen immunization delayed the initiation of clinical disease and dampened the severity of peak initial disease and relapses. Reduced EAE severity correlated with the reduction of pathology and leukocytes in the CNS, particularly, activated CD11b+Ly6Chi macrophages. There were no differences in effector T cell-proliferative responses or effector T cell IFN-γ or IL-17 responses. However, treatment at the onset of disease did not reduce disease progression. Treatment of adoptive T cell transfer recipient mice with anti-CCL22 resulted in decreased clinical disease development accompanied by a decrease in CNS accumulation of CD11b+Ly6Chi macrophages. Neutralization of CCL22 resulted in a macrophage population whose effector cytokine expression consisted of decreased TNF and increased IL-10, a phenotype more consistent with M2 macrophages. This was corroborated by in vitro cultures of macrophages with CCL22. These results suggest that CCL22 functions to regulate development of EAE through macrophage chemoattraction and effector function.

【 授权许可】

Unknown