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Responsible Editor | The imbalance of Enzyme's immune homeostasis can lead to the occurrence of autoimmune diseases.
Regulatory T cells (Tregs) are a subset of T cells that have the function of inducing and maintaining immune tolerance and can be used to treat imbalances in immune homeostasis.
However, the use of non-specific Tregs to treat autoimmune diseases in vivo may lead to systemic immune suppression.
Therefore, induction of antigen-specific Tregs is the best choice for disease treatment.
Although antigen-specific Tregs have shown certain therapeutic effects in animal models of autoimmune diseases, their positive clinical effects have not been widely reported.
This may be because in the inflammatory environment where T cells are over-activated in the disease state, Tregs can lose immunoregulatory activity, leading to treatment failure or disease recurrence.
Therefore, before using Tregs to establish a new immune homeostasis, too many activated T cells should be cleared first to break the imbalanced immune state.
Previous studies have used radiation to destroy the immune system or use antibodies to reduce activated T cells, but such methods have a great risk of off-target.
Therefore, there is an urgent need to establish a new strategy for sequential, safe and effective induction of antigen-specific Tregs and reconstruction of immune homeostasis.
On March 11, 2021, the team of Jin Yan and Liu Shiyu of the Air Force Military Medical University and the Chen Xin team of Xi’an Jiaotong University jointly published a research paper titled Modular immune-homeostatic microparticles promote immune tolerance in mouse autoimmune models on the cover of Science Translational Medicine.
This study successfully induced antigen-specific Tregs and immune tolerance in a variety of autoimmune disease models by constructing modular immune-regulating microspheres, and significantly alleviated disease symptoms.
In order to eliminate excessively activated T cells and induce Tregs in diseased individuals, the researchers synthesized a coupling monocyte chemotactic protein-1 (MCP-1), FasL and experimental autoimmune encephalomyelitis model (EAE) itself Antigen MOG35-55 immunomodulatory multi-level micro-nano materials (IHMs).
The hierarchical structure of IHMs can quickly release MCP-1 chemotactically activated T cells, and induce T cell apoptosis through FasL to clear the activated T cells in large quantities; subsequently, the phagocytosis of apoptotic cells by macrophages will promote TGF- The secretion of β promotes the differentiation of T cells into Tregs.
In the process of Tregs differentiation, MOG35-55 is further released, achieving the induction of antigen-specific Tregs in the EAE model.
The construction of IHMs is based on a modular design, in which the MCP-1 module, FasL module and MOG35-55 module can be replaced to meet the treatment needs of different diseases.
In order to verify this concept, the researchers replaced MOG35-55 with the autoantigen GAD524-543 or empty module of the type 1 diabetes model (NOD), and achieved antigen-specific/non-specific Tregs in the NOD model and enteritis model.
Induce.
Studies have found that by effectively removing excessively activated T cells and inducing the generation of Tregs, IHMs can significantly alleviate the symptoms of colitis in mouse colitis models, and at the same time significantly alleviate the symptoms of autoimmune diseases in EAE and NOD models.
In summary, this study successfully constructed a multi-level micro-nano material that induces immune tolerance by clearing activated T cells, and based on a modular design, it induces antigen-specific Tregs in different autoimmune disease models, which is a good candidate for autoimmune diseases.
Treatment provides new strategies.
IHMs induced antigen-specific immune tolerance pattern diagram.
In this study, Professor Jin Yan, Associate Professor Liu Shiyu, and Professor Chen Xin are the co-corresponding authors of the paper.
Chen Xin, Yang Xiaoshan (Ph.
D.
student at Air Force Military Medical University), Yuan Pingyun (Ph.
D.
, Xi’an Jiaotong University) Postgraduate) and Liu Shiyu are the co-first authors of the paper. Original link: https://stm.
sciencemag.
org/content/13/584/eaaw9668 Plate maker: Notes for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting without permission is prohibited.
The author has all legal rights, and offenders must be investigated.
Regulatory T cells (Tregs) are a subset of T cells that have the function of inducing and maintaining immune tolerance and can be used to treat imbalances in immune homeostasis.
However, the use of non-specific Tregs to treat autoimmune diseases in vivo may lead to systemic immune suppression.
Therefore, induction of antigen-specific Tregs is the best choice for disease treatment.
Although antigen-specific Tregs have shown certain therapeutic effects in animal models of autoimmune diseases, their positive clinical effects have not been widely reported.
This may be because in the inflammatory environment where T cells are over-activated in the disease state, Tregs can lose immunoregulatory activity, leading to treatment failure or disease recurrence.
Therefore, before using Tregs to establish a new immune homeostasis, too many activated T cells should be cleared first to break the imbalanced immune state.
Previous studies have used radiation to destroy the immune system or use antibodies to reduce activated T cells, but such methods have a great risk of off-target.
Therefore, there is an urgent need to establish a new strategy for sequential, safe and effective induction of antigen-specific Tregs and reconstruction of immune homeostasis.
On March 11, 2021, the team of Jin Yan and Liu Shiyu of the Air Force Military Medical University and the Chen Xin team of Xi’an Jiaotong University jointly published a research paper titled Modular immune-homeostatic microparticles promote immune tolerance in mouse autoimmune models on the cover of Science Translational Medicine.
This study successfully induced antigen-specific Tregs and immune tolerance in a variety of autoimmune disease models by constructing modular immune-regulating microspheres, and significantly alleviated disease symptoms.
In order to eliminate excessively activated T cells and induce Tregs in diseased individuals, the researchers synthesized a coupling monocyte chemotactic protein-1 (MCP-1), FasL and experimental autoimmune encephalomyelitis model (EAE) itself Antigen MOG35-55 immunomodulatory multi-level micro-nano materials (IHMs).
The hierarchical structure of IHMs can quickly release MCP-1 chemotactically activated T cells, and induce T cell apoptosis through FasL to clear the activated T cells in large quantities; subsequently, the phagocytosis of apoptotic cells by macrophages will promote TGF- The secretion of β promotes the differentiation of T cells into Tregs.
In the process of Tregs differentiation, MOG35-55 is further released, achieving the induction of antigen-specific Tregs in the EAE model.
The construction of IHMs is based on a modular design, in which the MCP-1 module, FasL module and MOG35-55 module can be replaced to meet the treatment needs of different diseases.
In order to verify this concept, the researchers replaced MOG35-55 with the autoantigen GAD524-543 or empty module of the type 1 diabetes model (NOD), and achieved antigen-specific/non-specific Tregs in the NOD model and enteritis model.
Induce.
Studies have found that by effectively removing excessively activated T cells and inducing the generation of Tregs, IHMs can significantly alleviate the symptoms of colitis in mouse colitis models, and at the same time significantly alleviate the symptoms of autoimmune diseases in EAE and NOD models.
In summary, this study successfully constructed a multi-level micro-nano material that induces immune tolerance by clearing activated T cells, and based on a modular design, it induces antigen-specific Tregs in different autoimmune disease models, which is a good candidate for autoimmune diseases.
Treatment provides new strategies.
IHMs induced antigen-specific immune tolerance pattern diagram.
In this study, Professor Jin Yan, Associate Professor Liu Shiyu, and Professor Chen Xin are the co-corresponding authors of the paper.
Chen Xin, Yang Xiaoshan (Ph.
D.
student at Air Force Military Medical University), Yuan Pingyun (Ph.
D.
, Xi’an Jiaotong University) Postgraduate) and Liu Shiyu are the co-first authors of the paper. Original link: https://stm.
sciencemag.
org/content/13/584/eaaw9668 Plate maker: Notes for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting without permission is prohibited.
The author has all legal rights, and offenders must be investigated.
