Differing Outcome of Experimental Autoimmune Encephalitis in Macrophage/Neutrophil- and T Cell-Specific gp130-Deficient Mice

Frontiers in Immunology
Kristian HolzChristoph Hölscher

Abstract

gp130 cytokines are differentially involved in regulating the T helper (H) 17-driven pathogenesis of experimental autoimmune encephalomyelitis (EAE), the animal model of human multiple sclerosis. Interleukin (IL)-6 directly promotes the development of TH17 cells through the gp130/IL-6R complex. By contrast, IL-27 has been shown to suppress a TH17 immune response by gp130/IL-27R-alpha (α) receptor ligation. The IL-27-dependent regulation of a TH17 development could be mediated on the level of CD4 T cells. However, because IL-27 also suppresses the secretion of the TH17-driving cytokines IL-6 and IL-12/23p40 in accessory cells, TH17 immune responses may also be controlled by IL-27 on the level of macrophages and/or neutrophils. To analyze these opposing effects of gp130 engagement on the pathogenesis of EAE, we immunized CD4+ T cell-specific gp130-deficient (CD4creposgp130loxP/loxP) and macrophage/neutrophil-specific gp130-deficient (LysMcreposgp130loxP/loxP) mice with the myelin-oligodendrocyte-glycoprotein peptide MOG35-55. Whereas inflammatory immune responses, TH17 differentiation, and pathology in CD4creposgp130loxP/loxP mice were mitigated, disease progression was eventually enhanced in LysMcreposgp130loxP/loxP mice. Exacer...Continue Reading

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Citations

Sep 25, 2019·Infection and Immunity·Jeongho ParkChristopher A Hunter
Jun 11, 2019·Frontiers in Immunology·Wen-Tao MaDe-Kun Chen
Nov 27, 2018·Biochemistry. Biokhimii︠a︡·V S GogolevaS A Nedospasov
Jun 22, 2021·Frontiers in Immunology·Nur Diyana Mohd ShukriKah Keng Wong

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Methods Mentioned

BETA
flow cytometry
PCR
density gradient centrifugation
FCS

Software Mentioned

cell

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