Thymic stromal lymphopoietin deficiency attenuates experimental autoimmune encephalomyelitis

Abstract

© 2015 British Society for Immunology. In the present study we examined the role of thymic stromal lymphopoietin (TSLP) in experimental autoimmune encephalomyelitis (EAE). Here, we report that TSLP knock-out (KO) mice display a delayed onset of disease and an attenuated form of EAE. This delayed onset was accompanied by a reduced number of encephalitogenic T helper type 1 (Th1) cells in the central nervous system (CNS) of TSLP KO mice. In addition, CD4+ and CD8+ T cells from CNS of TSLP KO mice show a reduced activation status in comparison to wild-type mice. It is noteworthy that we could also show that lymph node cells from TSLP KO mice expanded less efficiently and that interleukin (IL)-6-, interferon (IFN)-γ and tumour necrosis factor (TNF)-α levels were reduced. Furthermore, CD3+ T cells isolated in the preclinical phase from myelin oligodendrocyte glycoprotein peptide 35-55 (MOG35-55)-immunized TSLP KO mice showed a reduced response after secondary exposure to MOG35-55, indicating that differentiation of naive T cells into MOG35-55-specific effector and memory T cells was impaired in KO mice. The addition of recombinant TSLP enhanced T cell proliferation during MOG35-55 restimulation, showing that T cells also respond directly to TSLP. In summary, these data demonstrate that expression of, and immune activation by, TSLP contributes significantly to the immunopathology of EAE.