| First Author | Li H | Year | 2023 |
| Journal | Immunobiology | Volume | 228 |
| Issue | 3 | Pages | 152383 |
| PubMed ID | 37043976 | Mgi Jnum | J:367529 |
| Mgi Id | MGI:8209788 | Doi | 10.1016/j.imbio.2023.152383 |
| Citation | Li H, et al. (2023) Ubiquitin-specific protease 34 in macrophages limits CD8 T cell-mediated onset of vitiligo in mice. Immunobiology 228(3):152383 |
| abstractText | 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. |
