title: 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.
authors.affiliation: Department of Immune Modulation at the Department of Dermatology.
authors.forename: J
authors.initials: J
authors.lastname: Eckhardt
authors.affiliation: Department of Immune Modulation at the Department of Dermatology.
authors.forename: M
authors.initials: M
authors.lastname: Döbbeler
authors.affiliation: Department of Immune Modulation at the Department of Dermatology.
authors.forename: C
authors.initials: C
authors.lastname: König
authors.affiliation: Department of Immune Modulation at the Department of Dermatology.
authors.forename: K
authors.initials: K
authors.lastname: Kuczera
authors.affiliation: Department of Immune Modulation at the Department of Dermatology.
authors.forename: C
authors.initials: C
authors.lastname: Kuhnt
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Ostalecki
authors.affiliation: Department of Immune Modulation at the Department of Dermatology.
authors.forename: E
authors.initials: E
authors.lastname: Zinser
authors.affiliation: The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: T W
authors.initials: TW
authors.lastname: Mak
authors.affiliation: Department of Immune Modulation at the Department of Dermatology.
authors.forename: A
authors.initials: A
authors.lastname: Steinkasserer
authors.affiliation: Department of Immune Modulation at the Department of Dermatology.
authors.forename: M
authors.initials: M
authors.lastname: Lechmann
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C445081:myelin oligodendrocyte glycoprotein (35-55); D007371:Interferon-gamma; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
keywords: EAE; T cells; TSLP; autoimmunity