Depletion of PD-1-positive cells ameliorates autoimmune disease

Zhao, Peng; Wang, Peng; Dong, Shuyun; Zhou, Zemin; Cao, Yanguang; Yagita, Hideo; Xiao, He; Zheng, Song Guo; Fisher, Simon J.; Fujinami, Robert S.; Chen, Mingnan

doi:10.1038/s41551-019-0360-0

Cited by 56 publications

(54 citation statements)

References 65 publications

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“…A recent study has suggested that the depletion of PD-1 + cells using an anti-PD-1 coupled to immunotoxin helps controlling autoimmune diseases 55 . Alternatively, we hypothesized that the development of a PD-1 agonist has the potential to exploit PD-1 inhibitory signals to specifically inhibit highly activated immune cells.…”

Section: Discussionmentioning

confidence: 99%

PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity

et al. 2020

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Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 (Th2) cytokines that promote AHR and lung inflammation. As the programmed cell death protein-1 (PD-1) inhibitory axis regulates a variety of immune responses, here we investigate PD-1 function in pulmonary ILC2s during IL-33-induced airway inflammation. PD-1 limits the viability of ILC2s and downregulates their effector functions. Additionally, PD-1 deficiency shifts ILC2 metabolism toward glycolysis, glutaminolysis and methionine catabolism. PD-1 thus acts as a metabolic checkpoint in ILC2s, affecting cellular activation and proliferation. As the blockade of PD-1 exacerbates AHR, we also develop a human PD-1 agonist and show that it can ameliorate AHR and suppresses lung inflammation in a humanized mouse model. Together, these results highlight the importance of PD-1 agonistic treatment in allergic asthma and underscore its therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity

et al. 2020

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“…To date, hundreds of diverse IT constructs have been developed against diverse indications, such as B-or T-cell cancers, 25 solid tumors, 26 graft-versus-host disease, 27 viral infections, 28,29 and autoimmune diseases. 30 Numerous clinical trials of ITs have been conducted and are under way. 7 Nonetheless, only 3 ITs have been approved for human use thus far (Fig.…”

Section: Its Clinically Approved and Its In Clinical Trialsmentioning

confidence: 99%

Critical Issues in the Development of Immunotoxins for Anticancer Therapy

Kim

Jun

Kim

2020

Journal of Pharmaceutical Sciences

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“…Therefore, not only the coverage of disease-associated antigens but also the molecular weight and spatial epitope of each antigen should be considered in the design and construction of effective CAARs to treat such diseases. Recently we observed that the depletion of PD1 + cells mainly removes autoreactive cells and results in a therapeutic effect in several animal models of inflammatory diseases (76), providing an encouraging approach to combat autoimmune diseases.…”

Section: Strategy 2: Adoptive Immunotherapy To Eliminate Autoreactivementioning

confidence: 99%

Prospects of the Use of Cell Therapy to Induce Immune Tolerance

et al. 2020

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Conditions in which abnormal or excessive immune responses exist, such as autoimmune diseases (ADs), graft-versus-host disease, transplant rejection, and hypersensitivity reactions, are serious hazards to human health and well-being. The traditional immunosuppressive drugs used to treat these conditions can lead to decreased immune function, a higher risk of infection, and increased tumor susceptibility. As an alternative therapeutic approach, cell therapy, in which generally intact and living cells are injected, grafted, or implanted into a patient, has the potential to overcome the limitations of traditional drug treatment and to alleviate the symptoms of many refractory diseases. Cell therapy could be a powerful approach to induce immune tolerance and restore immune homeostasis with a deeper understanding of immune tolerance mechanisms and the development of new techniques. The purpose of this review is to describe the current panoramic scope of cell therapy for immune-mediated disorders, discuss the advantages and disadvantages of different types of cell therapy, and explore novel directions and future prospects for these tolerogenic therapies.

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Depletion of PD-1-positive cells ameliorates autoimmune disease

Cited by 56 publications

References 65 publications

PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity

PD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity

Critical Issues in the Development of Immunotoxins for Anticancer Therapy

Prospects of the Use of Cell Therapy to Induce Immune Tolerance

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