Amelioration of experimental autoimmune encephalomyelitis in IL-4Ralpha-/- mice implicates compensatory up-regulation of Th2-type cytokines.
The cytokine receptor interleukin (IL)-4R, expressed by lymphocytes, is well known for its role in immunomodulatory signaling and has also been documented on oligodendrocytes, suggesting involvement in glial cell interactions. In the present study, we investigated the clinical course and pathology of experimental autoimmune encephalomyelitis in mice demonstrating deletion of IL-4R and found a correlation with cytokine expression during acute and chronic disease. Wild-type (WT) littermates served as controls. Although IL-4R(-/-) mice displayed a milder course throughout, they showed comparable pathology to WT in the acute phase. However, during the chronic phase, IL-4R(-/-) mice exhibited extensive remyelination and an apparent increase in oligodendrocytes. Cytokine patterns were examined by immunocytochemistry, fluorescence-activated cell sorting, and enzyme-linked immunosorbent assay and were strongly proinflammatory within the central nervous system during the acute phase in WT mice whereas IL-4R(-/-) animals expressed higher levels of IL-6 and IL-10 that became more pronounced with time. The milder experimental autoimmune encephalomyelitis and enhanced remyelination in IL-4R(-/-) mice appeared to be related to a shift toward a Th-2 pattern involving mainly IL-6 and IL-10. These data suggest that IL-4R exerts a negative regulatory role on oligodendrocytes that when deleted results in enhanced myelin repair.
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Stefanie
S
Gaupp
Barbara
B
Cannella
Cedric S
CS
Raine
D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000172:deficiency* / Q000235:genetics; D018418:Th2 Cells / Q000276:immunology*; D015854:Up-Regulation; D053662:Interleukin-4 Receptor alpha Subunit
D016207:Cytokines; D016753:Interleukin-10; D015850:Interleukin-6; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit