Universität zu Köln

Schmidt, Thomas, Willenborg, Sebastian, Huenig, Thomas, Deeg, Cornelia A., Sonderstrup, Grete, Hertl, Michael and Eming, Ruediger (2016). Induction of T regulatory cells by the superagonistic anti-CD28 antibody D665 leads to decreased pathogenic IgG autoantibodies against desmoglein 3 in a HLA-transgenic mouse model of pemphigus vulgaris. Exp. Dermatol., 25 (4). S. 293 - 299. HOBOKEN: WILEY-BLACKWELL. ISSN 1600-0625

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Abstract

Pemphigus vulgaris (PV) is a potentially life-threatening autoimmune disease of the skin and mucous membranes. Its pathogenesis is based on IgG autoantibodies that target the desmosomal cadherins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1) and induce intra-epidermal loss of adhesion. Although the PV pathogenesis is well-understood, therapeutic options are still limited to immunosuppressive drugs, particularly corticosteroids, which are associated with significant side effects. Dsg3-reactive T regulatory cells (Treg) have been previously identified in PV and healthy carriers of PV-associated HLA class II alleles. Ex vivo, Dsg3-specific Treg cells down-regulated the activation of pathogenic Dsg3-specific T-helper (Th) 2 cells. In this study, in a HLA-DRB1*04:02 transgenic mouse model of PV, peripheral Treg cells were modulated by the use of Treg-depleting or expanding monoclonal antibodies, respectively. Our findings show that, in vivo, although not statistically significant, Treg cells exert a clear down-regulatory effect on the Dsg3-driven T-cell response and, accordingly, the formation of Dsg3-specific IgG antibodies. These observations confirm the powerful immune regulatory functions of Treg cells and identify Treg cells as potential therapeutic modulators in PV.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schmidt, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Willenborg, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Huenig, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Deeg, Cornelia A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Sonderstrup, Grete UNSPECIFIED UNSPECIFIED UNSPECIFIED Hertl, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Eming, Ruediger UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-280082
DOI:	10.1111/exd.12919
Journal or Publication Title:	Exp. Dermatol.
Volume:	25
Number:	4
Page Range:	S. 293 - 299
Date:	2016
Publisher:	WILEY-BLACKWELL
Place of Publication:	HOBOKEN
ISSN:	1600-0625
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSCRIPTION FACTOR FOXP3; CD28 SUPERAGONIST; MONOCLONAL-ANTIBODY; TGN1412 TRIAL; DISEASE; ANTIGEN; AUTOIMMUNITY; HOMEOSTASIS; EXPRESSION; TOLERANCE Multiple languages Dermatology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28008