Thymic stromal lymphopoietin deficiency attenuates experimental autoimmune encephalomyelitis

Summary 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.