Universität zu Köln

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

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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
Creators:	Creators Email ORCID ORCID Put Code Smith, R. E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Reyes, N. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Khandelwal, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlereth, S. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lee, H. S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Masli, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Saban, D. R. UNSPECIFIED UNSPECIFIED UNSPECIFIED
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
Uncontrolled Keywords:	Keywords Language GROWTH-FACTOR-BETA; IMMUNE-MEDIATED BLEPHAROCONJUNCTIVITIS; OCULAR SURFACE INFLAMMATION; VERNAL CONJUNCTIVITIS; IN-VIVO; ATOPIC KERATOCONJUNCTIVITIS; CYTOKINE PRODUCTION; INTERFERON-GAMMA; MURINE MODEL; MAST-CELLS Multiple languages Cell Biology; Hematology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26855