PMID- 33687107
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220322
IS  - 1600-0625 (Electronic)
IS  - 0906-6705 (Linking)
VI  - 30
IP  - 6
DP  - 2021 Jun
TI  - NKG2D and its ligands as cytotoxic factors in cutaneous lupus erythematosus.
PG  - 847-852
LID - 10.1111/exd.14311 [doi]
AB  - 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.
CI  - (c) 2021 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.
FAU - Vorwerk, Gero
AU  - Vorwerk G
AD  - Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
FAU - Zahn, Sabine
AU  - Zahn S
AD  - Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
FAU - Bieber, Thomas
AU  - Bieber T
AD  - Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
FAU - Wenzel, Joerg
AU  - Wenzel J
AUID- ORCID: 0000-0002-4744-5993
AD  - Department of Dermatology and Allergy, University of Bonn, Bonn, Germany.
LA  - eng
PT  - Journal Article
DEP - 20210309
PL  - Denmark
TA  - Exp Dermatol
JT  - Experimental dermatology
JID - 9301549
RN  - 0 (Cytotoxins)
RN  - 0 (KLRK1 protein, human)
RN  - 0 (Ligands)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily K)
SB  - IM
MH  - Cytotoxins/*metabolism
MH  - Humans
MH  - Immunity, Innate/genetics
MH  - Keratinocytes/*metabolism
MH  - Ligands
MH  - Lupus Erythematosus, Cutaneous/*metabolism
MH  - NK Cell Lectin-Like Receptor Subfamily K/genetics/*metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - MICB
OT  - cell stress
OT  - innate immunity
OT  - interferon
OT  - skin
EDAT- 2021/03/10 06:00
MHDA- 2022/03/23 06:00
CRDT- 2021/03/09 08:40
PHST- 2021/01/09 00:00 [revised]
PHST- 2020/06/06 00:00 [received]
PHST- 2021/02/15 00:00 [accepted]
PHST- 2021/03/10 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
PHST- 2021/03/09 08:40 [entrez]
AID - 10.1111/exd.14311 [doi]
PST - ppublish
SO  - Exp Dermatol. 2021 Jun;30(6):847-852. doi: 10.1111/exd.14311. Epub 2021 Mar 9.