Thymic stromal lymphopoietin deficiency attenuates experimental autoimmune encephalomyelitis.

Abstract:

: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 (MOG(35-55))-immunized TSLP KO mice showed a reduced response after secondary exposure to MOG(35-55), indicating that differentiation of naive T cells into MOG(35-55)-specific effector and memory T cells was impaired in KO mice. The addition of recombinant TSLP enhanced T cell proliferation during MOG(35-55) 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.

journal_name

Clin Exp Immunol

authors

Eckhardt J,Döbbeler M,König C,Kuczera K,Kuhnt C,Ostalecki C,Zinser E,Mak TW,Steinkasserer A,Lechmann M

doi

10.1111/cei.12621

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

51-64

issue

1

eissn

0009-9104

issn

1365-2249

journal_volume

181

pub_type

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