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NKG2D and its ligands as cytotoxic factors in cutaneous lupus erythematosus
- Source :
- Experimental Dermatology. 30:847-852
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Cutaneous lupus erythematosus (CLE) is an autoimmune skin disorder that is characterized by an anti-epidermal lymphocytic infiltrate invading the dermo-epidermal junction, causing an interface dermatitis (ID). Pathogenesis of CLE has been linked to activation of innate immunity. NKG2D is an innate immune receptor on NK cells and distinct T-cell populations. The NKG2D ligands MHC class I polypeptide-related sequence A and B (MICA, MICB) have been associated to CLE susceptibility. Our gene microarray analyses of chronic discoid lupus erythematosus (CDLE) skin lesions, separated in epidermal, junctional and dermal skin areas via laser microdissection, revealed a high expression of NKG2D in the lymphocytic infiltrate and led us to further investigate the role of NKG2D in CLE. Pathway analyses showed a strong "interferon (IFN) signature" and vast activation of innate immune response pathways (TLR, RIG-I, cytosolic DNA sensing, JAK/STAT) in CDLE, that expressed the high NKG2D signal. Immunohistochemistry (IHC) confirmed the presence of NKG2D and its ligand MICB in CDLE and subacute cutaneous lupus erythematosus (SCLE) lesions. Finally, HaCaT cells were stimulated with nucleic acids and extracted RNA was sequenced with Illumina HiSeq and showed that stressed keratinocytes express typical NKG2D ligands MICA/B and ULBP2. This study provides first evidence that NKG2D is present in CDLE and SCLE skin lesions and could be relevant for cytotoxicity in IFN-driven skin lesions with upregulated innate immune response pathways present in CLE. It could furthermore play a role in CLE inflammation promoted by keratinocytes under cell stress.
- Subjects :
- Keratinocytes
chemical and pharmacologic phenomena
Dermatology
Ligands
Biochemistry
Subacute cutaneous lupus erythematosus
Lymphocytic Infiltrate
Interferon
MHC class I
Lupus Erythematosus, Cutaneous
medicine
Humans
Cytotoxic T cell
Molecular Biology
Innate immune system
integumentary system
biology
Cytotoxins
medicine.disease
NKG2D
Immunity, Innate
Up-Regulation
ULBP2
NK Cell Lectin-Like Receptor Subfamily K
biology.protein
Cancer research
medicine.drug
Subjects
Details
- ISSN :
- 16000625 and 09066705
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Experimental Dermatology
- Accession number :
- edsair.doi.dedup.....48cadef879e2e7d2e5dae0fabd2ddb4e