Smith, R. E., Reyes, N. J., Khandelwal, P., Schlereth, S. L., Lee, H. S., Masli, S. and Saban, D. R. (2016). Secondary allergic T cell responses are regulated by dendritic cell-derived thrombospondin-1 in the setting of allergic eye disease. J. Leukoc. Biol., 100 (2). S. 371 - 381. BETHESDA: FEDERATION AMER SOC EXP BIOL. ISSN 1938-3673
Full text not available from this repository.Abstract
Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re-exposure, or secondary responses. However, molecular cues by dendritic cells underpinning allergic T cell response levels and the impact that this control has on consequent severity of allergic disease are poorly understood. Here, we show that a deficiency in thrombospondin-1, a matricellular protein known to affect immune function, has subsequent effects on downstream T cell responses during allergy, as revealed in an established mouse model of allergic eye disease. More specifically, we demonstrate that a thrombospondin-1 deficiency specific to dendritic cells leads to heightened secondary T cell responses and consequent clinical disease. Interestingly, whereas thrombospondin-1-deficient dendritic cells augmented activity of allergen-primed T cells, this increase was not recapitulated with naive T cells in vitro. The role of dendritic cell-derived thrombospondin-1 in regulating secondary allergic T cell responses was confirmed in vivo, as local transfer of thrombospondin-1-sufficient dendritic cells to the ocular mucosa of thrombospondin-1 null hosts prevented the development of augmented secondary T cell responses and heightened allergic eye disease clinical responses. Finally, we demonstrate that topical instillation of thrombospondin-1-derived peptide reduces T cell activity and clinical progression of allergic eye disease. Taken together, this study reveals an important modulatory role of dendritic cell-derived thrombospondin-1 on secondary allergic T cell responses and suggests the possible dysregulation of dendritic cell-derived thrombospondin-1 expression as a factor in allergic eye disease severity.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-268553 | ||||||||||||||||||||||||||||||||
DOI: | 10.1189/jlb.3A0815-357RR | ||||||||||||||||||||||||||||||||
Journal or Publication Title: | J. Leukoc. Biol. | ||||||||||||||||||||||||||||||||
Volume: | 100 | ||||||||||||||||||||||||||||||||
Number: | 2 | ||||||||||||||||||||||||||||||||
Page Range: | S. 371 - 381 | ||||||||||||||||||||||||||||||||
Date: | 2016 | ||||||||||||||||||||||||||||||||
Publisher: | FEDERATION AMER SOC EXP BIOL | ||||||||||||||||||||||||||||||||
Place of Publication: | BETHESDA | ||||||||||||||||||||||||||||||||
ISSN: | 1938-3673 | ||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/26855 |
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