Science: challenge the routine! Professor Chen Liping found that activation of pd-1h is hopeful for the treatment of lupus

December 26, 2019 / Biovalley BIOON / - -- the immune system has a series of regulatory factors designed to prevent it from attacking the host's own tissues However, when the complex checks and balances in the immune system are damaged, autoimmune diseases will occur Systemic lupus erythematosus (SLE) and discoid skin lupus erythematosus (DLE) are autoimmune diseases They are characterized by inappropriate immune responses to their own proteins, but the key factors determining the pathogenesis and progress of the disease are still largely unknown In the past decade, scientists have found that blocking the key regulators of the immune system can help activate the body's natural defense against various forms of cancer, thus ushering in a new era of cancer immunotherapy For example, immunocheckpoint blockers (also known as immunocheckpoint inhibitors) can effectively treat many cancers by blocking immunocheckpoint PD-1 or CTLA-4 on the surface of T cells Now, in a new study, researchers from Yale University in the U.S essentially overturned this view They created BALB / c mice lacking immunosuppressive receptor pd-1h (also known as Vista or b7-h5) through gene knockout, and found that these pd-1h knockout mice would produce systemic lupus similar to two human lupus forms, systemic lupus and cutaneous lupus Autoimmune diseases and skin autoimmune diseases, and more susceptible to the influence of the immunosuppression induced by pristane In systemic lupus, the immune system attacks many organs, while the typical feature of skin lupus is obvious skin deformity The related research results were recently published in the Journal of Science Translational Medicine The title of the paper is "pd-1h (Vista) - mediated suppression of autoimmunity in systematic and cubaneous lupus erythematosus" Skin samples from lupus patients showed increased gene activity in the immune system, pictured in Chen lab These findings suggest that pd-1h dysfunction may cause damage to the immune system of skin and organs, which is the typical feature of autoimmune disease lupus In addition, these pd-1h knock-out mice had plasma like dendritic cells (PDC) in their lupus lesions, similar to that in human discoid lupus erythematosus "Pd-1h is obviously involved in the inhibition of lupus, but it seems to be selective because it does not have the same role in several other autoimmune diseases," said Dr Lieping Chen, a Yale University professor of immunobiology, a Dermatology Professor and a medical professor Pd-1h is a more common homolog of PD-1, and PD-1 also helps to inhibit immune system response Professor Chen Liping is a pioneer in the identification and development of PD-1 inhibitors, which can activate T cells to attack many types of cancer Several laboratories have also tried to use pd-1h as a cancer treatment, but so far it has not been successful These findings suggest that pd-1h function is crucial in lupus patients, Chen said When its function is damaged, these patients are easily attacked by the immune system on the skin and multiple organs By using mass flow cytometry, Professor Chen and his team identified pro-inflammatory neutrophils as the crucial early immune infiltrating cells in the lesions of lupus erythematosus in mice lacking pd-1h They also found that pd-1h was highly expressed on the surface of immune cells in human systemic lupus erythematosus, cutaneous discoid lupus erythematosus lesions and cutaneous lupus lesions in MRL / lpr mice In MRL / lpr lupus mice, administration of mAb activating pd-1h reduced skin symptoms, some autoimmune markers including autoantibodies, inflammatory cytokines and chemokines, and decreased the proliferation of immune cells In addition, pd-1h on the surface of T cells and bone marrow cells (including neutrophils and pDCs) can transmit inhibitory signals, leading to the activation and function decline of T cells and bone marrow cells, which indicates that pd-1h is an inhibitory receptor on the surface of T cells and bone marrow cells According to these findings, they believe that pd-1h is a key factor in the pathogenesis and progression of lupus, and pd-1h activation may restore the immune balance in lupus patients, thus potentially effective treatment of systemic lupus and cutaneous lupus The researchers said the findings could help explain the origins of lupus and suggest new ways in which scientists might be able to restore the function of the regulator of this functional impairment and provide urgently needed new therapies for the treatment of lupus Professor Chen Liping said that currently there are very limited treatment options for lupus patients, but these new findings suggest that a method called protein fusion may mimic pd-1h and help control the immune system and fight the disease (Bio Valley bio Com) editor's comment: the reason why this new study thinks that breaking the routine is because in cancer immunotherapy, it is to reactivate the inhibited T cells and play the role of attacking cancer cells This new study just goes against the way, and treats autoimmune diseases by suppressing immune response In fact, it is well understood that in cancer, cancer cells act on the immunosuppressive receptor PD-1 or CTLA-4 on the surface of T cells, so that the immune response in vivo is inhibited Therefore, in order to treat cancer, it is necessary to inhibit PD-1 or CTLA-4, so as to activate the immune response of T cells In autoimmune diseases, the immune response is over active, so it is necessary to activate the immunosuppressive receptor pd-1h to suppress the over active immune response and restore the immune balance In short, in cancer, the immune response is insufficient and needs to be supplemented, while in autoimmune diseases, the immune response is overactive and needs to be suppressed Reference: 1 Xue Han et al Pd-1h (Vista) - mediated suppression of automation in systematic and cutaneous lupus every thematosus Science Translational Medicine, 2019, doi:10.1126/scitranslmed.aax1159 2.Flipping the script on novel cancer therapy leads to insights into lupus https://medicalxpress.com/news/2019-12-flipping-script-cancer-therapy-insights.html