LYG1 exerts antitumor function through promoting the activation, proliferation, and function of CD4⁺ T cells

Abstract

Identification of novel stimulatory cytokines with antitumor function would have great value in tumor immunotherapy investigations. Here, we report LYG1 (Lysozyme G-like 1) identified through the strategy of Immunogenomics as a novel classical secretory protein with tumor-inhibiting function. LYG1 recombinant protein (rhLYG1) could significantly suppress the growth of B16 tumors in WT B6 mice, but not in SCID-beige mice, Rag1 ¡/¡ mice, CD4 C -or CD8 C T cell-deleted mice. It could increase the number of CD4C and CD8 C T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes, and spleens, and promote IFNg production by T cells in tumor-bearing mice. In vitro experiments demonstrated that rhLYG1 could directly enhance IFNg secretion by CD4 C T cells, but not CD8 C T cells. Moreover, it could promote the activation, proliferation, and IFNg production of tumor antigen-specific CD4 C T cells. The tumor-inhibiting effect of LYG1 was eliminated in Ifng ¡/¡ mice. Furthermore, LYG1 deficiency accelerated B16 and LLC1 tumor growth and inhibited the function of T cells. In summary, our findings reveal a tumorinhibiting role for LYG1 through promoting the activation, proliferation, and function of CD4 C T cells in antitumor immune responses, offering implications for novel tumor immunotherapy.

CTRP4 acts as an anti‐inflammatory factor in macrophages and protects against endotoxic shock

“…To obtain sufficient recombinant protein with high quality, CTRP4 was stably overexpressed in CHO cells via transfection of pcDNA3.1‐B‐CTRP4 as previously described [37]. Supernatants were collected and purified by affinity chromatography using Ni‐Sepharose 6 Fast Flow column (GE Healthcare, 11–0008).…”

LYG1 Deficiency Attenuates the Severity of Acute Graft-Versus-Host Disease via Skewing Allogeneic T Cells Polarization Towards Treg Cells

“…CXCL9, CXCL10-CXCR3 interactions has been linked to activated T cell trafficking to aGVHD target organs in humans and mice ( 16 ). Our previous study found that rhLYG1 administration in mice can enhance the expression of T cell chemokines, including CCL5, CXCL9 and CXCL10, and infiltration of T cells in tumors ( 11 ). In this study, the decreased infiltration of allogeneic CD4 + T cells in the livers and lungs of mice that received Lyg1 -/- T cells, which maybe related that LYG1 deficiency inhibited the expression of CXCL9 and CXCL10, explained partially that LYG1 deficiency in donor T cells suppressed aGVHD.…”

“…Exogenous injection of IL-12 or IL-18 increased the expression of IFN-γ, thereby inducing the expression of Fas in donor T cells, leading to activation-induc,ed cell death, reducing donor T cells responses to host antigens and finally attenuating aGVHD ( 26 , 27 ). Our previous studies have shown that rhLYG1 can promote antigen specific activity and IFN-γ production of T lymphocytes in tumor models ( 11 ). In this study, we found inhibited activation of CD4 + T cells and IFN-γ expression of allogeneic T cells in mice receiving Lyg1 -/- donor T cells, whereas rhLYG1 administration aggravated aGVHD severity through promoting IFN-γ production of allogeneic T cells, more importantly, the absence of IFN-γ in donor T cells could partially abrogate rhLYG1-induced GVHD development, corroborating that the effect of LYG1 on aGVHD were mainly mediated by IFN-γ.…”

“…In our previous study, we have identified and characterized a novel classical secretory protein LYG1 (Lysozyme G-like 1) through immunogenomics strategy ( 11 ). Recombinant human LYG1 protein (rhLYG1) can inhibit tumor growth by promoting the activation and IFN-γ production of tumor antigen-specific CD4 + T cells ( 11 ). While LYG1 deficiency accelerated B16 and LLC1 tumor growth due to the inhibited T cell functions.…”

Unconventional effects of long-term storage of microwave-modified chicken egg white lysozyme preparations

“…However, the spectrum of the enzyme's antibacterial activity can be significantly expanded as a result of modifications leading to changes in the protein structure that cause its oligomerization and an increase in surface hydrophobicity 3 , 4 . The modified lysozyme also has antiviral 5 and antifungal 6 , 7 properties and stimulates the appropriate cells of the body to produce various bioactive compounds to obtain antitumour activity 4 , 8 . According to the latest reports, by stimulating the formation of interferon-β 4 , the enzyme may be an effective agent against the SARS-Cov-2 virus and thus help fight COVID-19 9 , 10 .…”