PMID- 37043976
OWN - NLM
STAT- MEDLINE
DCOM- 20230614
LR  - 20230615
IS  - 1878-3279 (Electronic)
IS  - 0171-2985 (Linking)
VI  - 228
IP  - 3
DP  - 2023 May
TI  - Ubiquitin-specific protease 34 in macrophages limits CD8 T cell-mediated onset of 
      vitiligo in mice.
PG  - 152383
LID - S0171-2985(23)00051-7 [pii]
LID - 10.1016/j.imbio.2023.152383 [doi]
AB  - As an autoimmune disorder, vitiligo is characterized by depigmented skin macules. 
      CD8(+)T cells and macrophages enrichment promote the onset of vitiligo, while the 
      role of macrophages to CD8(+)T is not well deciphered. To develop a mouse model 
      of vitiligo with prominent epidermal depigmentation, Krt14-Kitl* transgenic mice 
      containing an elevated number of melanocytes in the epidermis with membrane-bound 
      Kit ligand (Kitl*) were adoptively transferred with premelanosome protein (PMEL) 
      CD8(+) T cells. On the other hand, Krt14-Kitl* mice were mated with 
      ubiquitin-specific protease 34 (USP34)(MKO) mice to decipher the role of USP34 in 
      vitiligo. Vitiligo scores and PMEL CD8(+) T cell enrichment were detected with 
      flow cytometry. Human peripheral blood mononuclear cells (PBMCs) or mice bone 
      marrow-derived macrophages (BMDMs) were incubated with lipopolysaccharide (LPS), 
      CpG, or co-incubated with KU-55933, an ataxia telangiectasia-mutated (ATM) 
      inhibitor. Chemokine (C-C motif) ligand 2 (CCL2), Ccl5, and interleukin (Il)-12alpha 
      expression was assayed with real-time PCR, and p-IKKalpha/beta was assayed with Western 
      blots. USP34 was up-regulated in the PBMCs of vitiligo patients and 
      LPS-stimulated BMDMs. USP34 deficiency did not affect the differentiation of 
      CD11b(+)F4/80(+) macrophages in the bone marrow. Immunoprecipitation demonstrated 
      the interaction between USP34 and ATM. USP34 deficiency or KU-55933 
      administration promoted the induction of Ccl2, Ccl5, Il12alpha, and p-IKKalpha/beta in LPS 
      or CpG stimulated BMDMs; KU-55933 administration could not affect the expression 
      of the above molecules in USP34 deficient BMDMs. It further revealed that USP34 
      deficiency promoted the development of vitiligo with increased PMEL CD8(+) T cell 
      enrichment, which was not affected by KU-55933 administration. USP34 deficiency 
      in macrophages promotes the onset of vitiligo with increased PMEL CD8(+) T cell 
      enrichment, and USP34/ATM complex can be considered as a therapy target.
CI  - Copyright (c) 2023 Elsevier GmbH. All rights reserved.
FAU - Li, He
AU  - Li H
AD  - Department of Dermatology, the Affiliated Huaian No. 1 People's Hospital of 
      Nanjing Medical University, No. 1 Huanghe West Road, Huai'an 223300, Jiangsu, 
      China.
FAU - Li, Xiaoqing
AU  - Li X
AD  - Department of Dermatology, the Affiliated Huaian No. 1 People's Hospital of 
      Nanjing Medical University, No. 1 Huanghe West Road, Huai'an 223300, Jiangsu, 
      China.
FAU - Kong, Yinghui
AU  - Kong Y
AD  - Department of Dermatology, the Affiliated Huaian No. 1 People's Hospital of 
      Nanjing Medical University, No. 1 Huanghe West Road, Huai'an 223300, Jiangsu, 
      China.
FAU - Sun, Weiguo
AU  - Sun W
AD  - Department of Dermatology, the Affiliated Huaian No. 1 People's Hospital of 
      Nanjing Medical University, No. 1 Huanghe West Road, Huai'an 223300, Jiangsu, 
      China. Electronic address: sunwg1242@126.com.
LA  - eng
PT  - Journal Article
DEP - 20230408
PL  - Netherlands
TA  - Immunobiology
JT  - Immunobiology
JID - 8002742
RN  - EC 2.7.11.10 (I-kappa B Kinase)
RN  - 0 (Lipopolysaccharides)
RN  - EC 3.4.19.12 (Ubiquitin-Specific Proteases)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Vitiligo/metabolism
MH  - CD8-Positive T-Lymphocytes
MH  - I-kappa B Kinase
MH  - Leukocytes, Mononuclear/metabolism
MH  - Lipopolysaccharides/metabolism
MH  - Mice, Transgenic
MH  - Ubiquitin-Specific Proteases/metabolism
OTO - NOTNLM
OT  - ATM
OT  - CD8(+) T
OT  - Macrophages
OT  - USP34
OT  - Vitiligo
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/04/13 06:00
MHDA- 2023/06/14 06:42
CRDT- 2023/04/12 18:06
PHST- 2022/12/10 00:00 [received]
PHST- 2023/03/30 00:00 [revised]
PHST- 2023/04/04 00:00 [accepted]
PHST- 2023/06/14 06:42 [medline]
PHST- 2023/04/13 06:00 [pubmed]
PHST- 2023/04/12 18:06 [entrez]
AID - S0171-2985(23)00051-7 [pii]
AID - 10.1016/j.imbio.2023.152383 [doi]
PST - ppublish
SO  - Immunobiology. 2023 May;228(3):152383. doi: 10.1016/j.imbio.2023.152383. Epub 
      2023 Apr 8.