Amelioration of experimental autoimmune encephalomyelitis in IL-4Rα-/- mice implicates compensatory up-regulation of Th2-type cytokines

Stefanie Gaupp, Barbara Cannella, Cedric S. Raine

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalAmerican Journal of Pathology
Volume173
Issue number1
DOIs
StatePublished - Jul 2008

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Autoimmune Experimental Encephalomyelitis
Interleukins
Up-Regulation
Cytokines
Oligodendroglia
Interleukin-10
Interleukin-6
Cytokine Receptors
Clinical Pathology
Acute Disease
Myelin Sheath
Cell Communication
Neuroglia
Flow Cytometry
Chronic Disease
Central Nervous System
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Lymphocytes
Pathology

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Amelioration of experimental autoimmune encephalomyelitis in IL-4Rα-/- mice implicates compensatory up-regulation of Th2-type cytokines. / Gaupp, Stefanie; Cannella, Barbara; Raine, Cedric S.

In: American Journal of Pathology, Vol. 173, No. 1, 07.2008, p. 119-129.

Research output: Contribution to journalArticle

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