The transcription factor CSL homolog in Penaeus vannamei positively regulates the transcription of the hemocyanin small subunit gene.

Hemocyanin, a copper-containing respiratory protein, is abundantly present in hemolymph of arthropods and mollusks and performs a variety of immunological functions. However, the regulatory mechanisms of hemocyanin gene transcription remain largely unclear. Our previous work showed that knockdown of the transcription factor CSL, a component of the Notch signaling pathway, downregulated the expression of Penaeus vannamei hemocyanin small subunit gene (PvHMCs), indicating the involvement of CSL in regulating the PvHMCs transcription. In this study, we identified a CSL binding motif ("GAATCCCAGA", +1675/+1684 bp) in the core promoter of PvHMCs (designated as HsP3). Dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA) demonstrated that the CSL homolog in P. vannamei (PvCSL) could directly bind and activate the HsP3 promoter. Moreover, in vivo silencing of PvCSL significantly attenuated the mRNA and protein expression of PvHMCs. Finally, in response to Vibrio parahaemolyticus, Streptococcus iniae and white spot syndrome virus (WSSV) challenge, the transcript of PvCSL and PvHMCs showed a positive correlation, suggesting that PvCSL could also modulate the expression of PvHMCs upon pathogen stimulation. Taken together, our present finding is the first to demonstrate that PvCSL is a crucial factor in transcriptional control of PvHMCs.

Periostin deficiency reduces PD-1+ tumor-associated macrophage infiltration and enhances anti-PD-1 efficacy in colorectal cancer.

Periostin, a multifunctional extracellular protein, plays an important role in inflammatory disorders and tumorigenesis. Our previous work has demonstrated that periostin deficiency inhibits colorectal cancer (CRC) progression. Here, we aim to clarify the role of periostin in the immune microenvironment of CRC. We find that periostin deficiency significantly decreases the infiltration of programmed death receptor 1 (PD-1)+ tumor-associated macrophages (TAMs) in CRC tissues. Periostin promotes the expression of PD-1 on TAMs by integrin-ILK-nuclear factor κB (NF-κB) signaling, and PD-1+ TAMs produce interleukin-6 (IL-6) and interferon γ (IFN-γ) to induce the expression of PD-L1 on colorectal tumor cells. Moreover, combined inhibition of periostin and PD-1 significantly suppresses CRC progression compared with the inhibition of periostin or PD-1 alone. In summary, our results suggest that periostin deficiency reduces the infiltration of PD-1+ TAMs and enhances the efficacy of anti-PD-1 treatment in CRC.