The anti-inflammatory role of zDHHC23 through the promotion of macrophage M2 polarization and macrophage necroptosis in large yellow croaker ( Larimichthys crocea ).

Zinc finger Asp-His-His-Cys motif-containing (zDHHC) proteins, known for their palmitoyltransferase (PAT) activity, play crucial roles in diverse cellular processes, including immune regulation. However, their non-palmitoyltransferase immunomodulatory functions and involvement in teleost immune responses remain underexplored. In this study, we systematically characterized the zDHHC family in the large yellow croaker ( Larimichthys crocea ), identifying 22 members. Phylogenetic analysis unveiled that each of the 22 Lc zDHHCs formed distinct clusters with their orthologues from other teleost species. Furthermore, all Lc zDHHCs exhibited a highly conserved DHHC domain, as confirmed by tertiary structure prediction. Notably, Lc zDHHC23 exhibited the most pronounced upregulation following Pseudomonas plecoglossicida ( P. plecoglossicida ) infection of macrophage/monocyte cells (MO/MΦ). Silencing Lc zDHHC23 led to heightened pro-inflammatory cytokine expression and diminished anti-inflammatory cytokine levels in MO/MΦ during infection, indicating its anti-inflammatory role. Functionally, Lc zDHHC23 facilitated M2-type macrophage polarization, as evidenced by a significant skewing of MO/MΦ towards the pro-inflammatory M1 phenotype upon Lc zDHHC23 knockdown, along with the inhibition of MO/MΦ necroptosis induced by P. plecoglossicida infection. These findings highlight the non-PAT immunomodulatory function of Lc zDHHC23 in teleost immune regulation, broadening our understanding of zDHHC proteins in host-pathogen interactions, suggesting Lc zDHHC23 as a potential therapeutic target for immune modulation in aquatic species.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Dai, Zhao, Zhu, Fei, Nie and Chen.)