Transplantable programmed death ligand 1 expressing gastroids from gastric cancer prone Nfkb1-/- mice.
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ABSTRACT:
SUBMITTER: Low JT
PROVIDER: S-EPMC8599488 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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Transplantable programmed death ligand 1 expressing gastroids from gastric cancer prone Nfkb1<sup>-/-</sup> mice.
Low Jun T JT Ho Gwo-Yaw GY Scott Mark M Tan Chin Wee CW Whitehead Lachlan L Barber Kathy K Yip Hon Y K HYK Dekkers Johanna F JF Hirokawa Yumiko Y Silke John J Burgess Antony W AW Strasser Andreas A Putoczki Tracy L TL O'Reilly Lorraine A LA
Cell death & disease 20211117 12
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Project description:IntroductionChronic infections lead to the functional exhaustion of T cells. Exhausted T cells are phenotypically differentiated by the surface expression of the immunoinhibitory receptor, such as programmed death-1 (PD-1). The inhibitory signal is produced by the interaction between PD-1 and its PD-ligand 1 (PD-L1) and impairs the effector functions of T cells. However, the expression dynamics of PD-L1 and the immunological functions of the PD-1/PD-L1 pathway in chronic diseases of pigs are still poorly understood. In this study, we first analyzed the expression of PD-L1 in various chronic infections in pigs, and then evaluated the immune activation by the blocking assay targeting the swine PD-1/PD-L1 pathway.MethodsIn the initial experiments, anti-bovine PD-L1 monoclonal antibodies (mAbs) were tested for cross-reactivity with swine PD-L1. Subsequently, immunohistochemical analysis was conducted using the anti-PD-L1 mAb. Finally, we assessed the immune activation of swine peripheral blood mononuclear cells (PBMCs) by the blockade with anti-PD-L1 mAb.ResultsSeveral anti-PD-L1 mAbs tested recognized swine PD-L1-expressing cells. The binding of swine PD-L1 protein to swine PD-1 was inhibited by some of these cross-reactive mAbs. In addition, immunohistochemical analysis revealed that PD-L1 was expressed at the site of infection in chronic infections of pigs. The PD-L1 blockade increased the production of interleukin-2 from swine PBMCs.ConclusionsThese findings suggest that the PD-1/PD-L1 pathway could be also involved in immunosuppression in chronic infections in pigs. This study provides a new perspective on therapeutic strategies for chronic diseases in pigs by targeting immunosuppressive pathways.
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