Enhanced T cell proliferation, Th17 differentiation and unaltered IL-10 production lead to marginally enhanced development of experimental autoimmune encephalomyelitis in EBI3-deficient mice (114.12)

Abstract

Abstract Epstein-Barr virus-induced gene 3 (EBI3) encoded protein can form heterodimers with IL-27P28 and IL-12P35 to form IL-27 and IL-35. IL-27 and IL-35 may influence autoimmunity through inhibiting Th17 differentiation, and facilitating the inhibitory roles of Foxp3+ Treg cells, repectively. In this study we have evaluated the development of experimental autoimmune encephalomyelitis (EAE) in EBI3-deficient mice that lack both IL-27 and IL-35. We found that MOG peptide immunization resulted in marginally enhanced EAE development in EBI3-deficient C57BL6 and 2D2 TCR transgenic mice. EBI3-deficiency resulted in significantly increased proliferation and Th17 differentiation of MOG-specific CD4 T cells in the peripheral lymphoid organs and in the central nervous system (CNS). However, IL-10 production was not affected or even enhanced in the peripheral lymphoid organs or the CNS of EBI3-deficient mice. Treg cells from EBI3-deficient 2D2 mice had reduced capacity of inhibiting proliferation of 2D2 T cells. Taken together, we have found that EBI3-deficiency results in marginally enhanced EAE severity, which is associated with enhanced T cell proliferation and Th17 differentiation. However, the relatively milder EAE enhancement and lack of impact on IL-10 production by EBI3-deficiency suggest that alternative signaling pathways (presumably IL27P28-related) can partially compensate for EBI3-deficiency in EBI3-/- mice.