PMID- 33651436
OWN - NLM
STAT- MEDLINE
DCOM- 20210630
LR  - 20210630
IS  - 1529-8019 (Electronic)
IS  - 1396-0296 (Linking)
VI  - 34
IP  - 3
DP  - 2021 May
TI  - A20 deficiency in myeloid cells deteriorates the onset of vitiligo in mice.
PG  - e14923
LID - 10.1111/dth.14923 [doi]
AB  - Melanocyte-specific CD8(+) T cells enrichment correlates with the severity of 
      vitiligo, and the role of A20 derived from myeloid cells in the enrichment of 
      pathogenic T cells is unknown. Premelanosome (PMEL)-specific transgenic CD8(+) T 
      cells were adoptive transferred into Krt14-Kitl* mice to construct the vitiligo 
      model, which was further mated with A20(MKO) mice and IKK2(fl/fl) mice. Bone 
      marrow cells were stimulated with 30% L929 cell-conditioned medium, Fc-human 
      tumor necrosis factor, and lipopolysaccharides to induce bone marrow-derived 
      macrophages (BMDMs). The relative expression of CCL2, CCL5, and IL12A was 
      detected with real-time PCR, and nuclear factor kappa B (NFkappaB) related molecules 
      were detected with Western blots. Fluorescence-activated cell sorting (FACS) was 
      utilized to assay the percent of innate and adaptive immune cells in the spleen 
      and bone marrow, and CD45(+) T in the skin. Down-regulated A20 was detected in 
      the skin biopsies of vitiligo patients. A20 deficiency did not affect the 
      development of T cells, B cells, macrophages, and neutrophils. A20 negatively 
      regulated the induction of proinflammatory chemokines (CCL2, CCL5, and IL12A) and 
      NFkappaB-related molecule expression in BMDMs, which could be blocked by NFkappaB 
      knockout. It further revealed that A20 negatively regulated the onset of vitiligo 
      in mice with diminished CD45(+) cells enrichment, which could also be reversed by 
      NFkappaB knockout. A20 deficiency in myeloid cells could deteriorate the onset of 
      vitiligo in mice, and A20 can be considered as a treatment target.
CI  - (c) 2021 Wiley Periodicals LLC.
FAU - Li, He
AU  - Li H
AD  - Department of Dermatology, The Affiliated Huaian No. 1 People's Hospital of 
      Nanjing Medical University, Huai'an, Jiangsu, China.
FAU - Wang, Congpin
AU  - Wang C
AD  - Department of Pharmacy, Eye Ear Nose & Throat Hospital, Fudan University, 
      Shanghai, China.
FAU - Li, Xiaoqing
AU  - Li X
AD  - Department of Dermatology, The Affiliated Huaian No. 1 People's Hospital of 
      Nanjing Medical University, Huai'an, Jiangsu, China.
FAU - Kong, Yinghui
AU  - Kong Y
AD  - Department of Dermatology, The Affiliated Huaian No. 1 People's Hospital of 
      Nanjing Medical University, Huai'an, Jiangsu, China.
FAU - Sun, Weiguo
AU  - Sun W
AUID- ORCID: 0000-0002-7882-5809
AD  - Department of Dermatology, The Affiliated Huaian No. 1 People's Hospital of 
      Nanjing Medical University, Huai'an, Jiangsu, China.
LA  - eng
PT  - Journal Article
DEP - 20210311
PL  - United States
TA  - Dermatol Ther
JT  - Dermatologic therapy
JID - 9700070
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes
MH  - Humans
MH  - Macrophages
MH  - Mice
MH  - Myeloid Cells
MH  - Tumor Necrosis Factor alpha-Induced Protein 3
MH  - *Vitiligo/genetics
OTO - NOTNLM
OT  - A20
OT  - CCL2
OT  - CCL5
OT  - Vitiligo
OT  - macrophage
EDAT- 2021/03/03 06:00
MHDA- 2021/07/01 06:00
CRDT- 2021/03/02 12:17
PHST- 2021/02/14 00:00 [revised]
PHST- 2020/10/09 00:00 [received]
PHST- 2021/02/22 00:00 [accepted]
PHST- 2021/03/03 06:00 [pubmed]
PHST- 2021/07/01 06:00 [medline]
PHST- 2021/03/02 12:17 [entrez]
AID - 10.1111/dth.14923 [doi]
PST - ppublish
SO  - Dermatol Ther. 2021 May;34(3):e14923. doi: 10.1111/dth.14923. Epub 2021 Mar 11.