In Vitro Immunological Effects of CXCR3 Inhibitor AMG487 on Dendritic Cells

Qin, Chenchen; Liu, Huihui; Tang, Bo; Cao, Min; Yu, Zhengyu; Liu, Beichen; Liu, Wei; Dong, Yujun; Ren, Hanyun

doi:10.1007/s00005-020-00577-3

Cited by 3 publications

(3 citation statements)

References 38 publications

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“…Recent developments revealed a crucial role for the autophagy pathway and proteins in immunity, which control inflammation through regulatory interactions with innate immune signaling pathways [8,39,40]. To explore the effect CXCR3-mediated autophagy on innate immune-related proteins, the NF-κB signaling pathway was investigated in IPEC-J2 cells.…”

Section: Cxcr3 Inhibition Blocks the Nf-κb Signaling Pathway By Promo...mentioning

confidence: 99%

CXCR3 Inhibition Blocks the NF-κB Signaling Pathway by Elevating Autophagy to Ameliorate Lipopolysaccharide-Induced Intestinal Dysfunction in Mice

Zhang

Deng

Zhang

et al. 2023

Cells

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Autophagy is a cellular catabolic process in the evolutionarily conservative turnover of intracellular substances in eukaryotes, which is involved in both immune homeostasis and injury repairment. CXCR3 is an interferon-induced chemokine receptor that participates in immune regulation and inflammatory responses. However, CXCR3 regulating intestine injury via autophagy along with the precise underlying mechanism have yet to be elucidated. In the current study, we employed an LPS-induced inflammatory mouse model and confirmed that CXCR3 knockout significantly attenuates intestinal mucosal structural damage and increases tight junction protein expression. CXCR3 knockout alleviated the LPS-induced increase in the expression of inflammatory factors including TNF-α, IL-6, p-65, and JNK-1 and enhanced autophagy by elevating LC3II, ATG12, and PINK1/Parkin expression. Mechanistically, the function of CXCR3 regarding autophagy and immunity was investigated in IPEC-J2 cells. CXCR3 inhibition by AMG487 enhanced autophagy and reduced the inflammatory response, as well as blocked the NF-κB signaling pathway and elevated the expression of the tight junction protein marker Claudin-1. Correspondingly, these effects were abolished by autophagy inhibition with the selective blocker, 3-MA. Moreover, the immunofluorescence assay results further demonstrated that CXCR3 inhibition-mediated autophagy blocked p65 nuclear translocation, and the majority of Claudin-1 was located at the tight junctions. In conclusion, CXCR3 inhibition reversed LPS-induced intestinal barrier damage and alleviated the NF-κB signaling pathway via enhancing autophagy. These data provided a theoretical basis for elucidating the immunoregulatory mechanism by targeting CXCR3 to prevent intestinal dysfunction.

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Section: Cxcr3 Inhibition Blocks the Nf-κb Signaling Pathway By Promo...mentioning

confidence: 99%

CXCR3 Inhibition Blocks the NF-κB Signaling Pathway by Elevating Autophagy to Ameliorate Lipopolysaccharide-Induced Intestinal Dysfunction in Mice

Zhang

Deng

Zhang

et al. 2023

Cells

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“…Inhibiting C-X-C motif chemokine receptor 3 (CXCR3) through its inhibitor AMG487 can significantly inhibit the expression of PD-L2 under lipopolysaccharide (LPS) stimulation, which inhibits DC development. Subsequently, the expression of CD25, CD69, and IFN-γ production decreases, suggesting suppressed T-cell activation [72]. IFN-α/ANO9.…”

Section: Post-translational Regulationmentioning

confidence: 99%

“… Increased resistance of cetux monotherapy [ 21 ] Cell communication LPS/CXCR3 Upregulation Bone marrow dendritic cell CXCR3 increase PD-L2 expression to activate DCs development and suppress antigen-specific T cell activation. Suppressed DC-mediated immune response [ 72 ] FCP/TLR4 Upregulation Bone marrow dendritic cell TLR4 in mast cells induced IL-13 promote PD-L2 expression in DCs to promote Th2 cell reactivity. Sustained Th2 cell-mediated humoral immunity [ 75 ] CCL2/CCR2 Upregulation Oesophageal squamous cell carcinoma The CCL2-CCR2 axis promotes PD-L2 expression in TAMs to increase TAM accumulation, and infiltration and deplete the antitumor effector of T cells.…”

Section: Regulatory Mechanism Of Pd-l2mentioning

confidence: 99%

Evolving landscape of PD-L2: bring new light to checkpoint immunotherapy

Wang

Gao

et al. 2022

Br J Cancer

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Immune checkpoint blockade therapy targeting programmed cell death protein 1 (PD-1) has revolutionized the landscape of multiple human cancer types, including head and neck squamous carcinoma (HNSCC). Programmed death ligand-2 (PD-L2), a PD-1 ligand, mediates cancer cell immune escape (or tolerance independent of PD-L1) and predicts poor prognosis of patients with HNSCC. Therefore, an in-depth understanding of the regulatory process of PD-L2 expression may stratify patients with HNSCC to benefit from anti-PD-1 immunotherapy. In this review, we summarised the PD-L2 expression and its immune-dependent and independent functions in HNSCC and other solid tumours. We focused on recent findings on the mechanisms that regulate PD-L2 at the genomic, transcriptional, post-transcriptional, translational, and post-translational levels, also in intercellular communication of tumour microenvironment (TME). We also discussed the prospects of using small molecular agents indirectly targeting PD-L2 in cancer therapy. These findings may provide a notable avenue in developing novel and effective PD-L2-targeted therapeutic strategies for immune combination therapy and uncovering biomarkers that improve the clinical efficacy of anti-PD-1 therapies.

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