TY  - JOUR
AU  - Meister, Michael
AU  - Tounsi, Amel
AU  - Gaffal, Evelyn
AU  - Bald, Tobias
AU  - Papatriantafyllou, Maria
AU  - Ludwig, Julia
AU  - Pougialis, Georg
AU  - Bestvater, Felix
AU  - Klotz, Luisa
AU  - Moldenhauer, Gerhard
AU  - Tüting, Thomas
AU  - Hämmerling, Günter
AU  - Arnold, Bernd
AU  - Oelert, Thilo
TI  - Self-Antigen Presentation by Keratinocytes in the Inflamed Adult Skin Modulates T-Cell Auto-Reactivity.
JO  - The journal of investigative dermatology
VL  - 135
IS  - 8
SN  - 0022-202X
CY  - Amsterdam
PB  - Elsevier
M1  - DKFZ-2017-03118
SP  - 1996 - 2004
PY  - 2015
AB  - Keratinocytes have a pivotal role in the regulation of immune responses, but the impact of antigen presentation by these cells is still poorly understood, particularly in a situation where the antigen will be presented only in adult life. Here, we generated a transgenic mouse model in which keratinocytes exclusively present a myelin basic protein (MBP) peptide covalently linked to the major histocompatibility complex class II β-chain, solely under inflammatory conditions. In these mice, inflammation caused by epicutaneous contact sensitizer treatment resulted in keratinocyte-mediated expansion of MBP-specific CD4(+) T cells in the skin. Moreover, repeated contact sensitizer application preceding a systemic MBP immunization reduced the reactivity of the respective CD4(+) T cells and lowered the symptoms of the resulting experimental autoimmune encephalomyelitis. This downregulation was CD4(+) T-cell-mediated and dependent on the presence of the immune modulator Dickkopf-3. Thus, presentation of a neo self-antigen by keratinocytes in the inflamed, adult skin can modulate CD4(+) T-cell auto-aggression at a distal organ.
KW  - 4-ethoxymethylene-2-phenyl-2-oxazoline-5-one (NLM Chemicals)
KW  - Autoantigens (NLM Chemicals)
KW  - Cyclopropanes (NLM Chemicals)
KW  - Dkk3 protein, mouse (NLM Chemicals)
KW  - Intercellular Signaling Peptides and Proteins (NLM Chemicals)
KW  - Myelin Basic Protein (NLM Chemicals)
KW  - Oxazoles (NLM Chemicals)
KW  - diphenylcyclopropenone (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25835957
DO  - DOI:10.1038/jid.2015.130
UR  - https://inrepo02.dkfz.de/record/127092
ER  -