Scientists in China have made important discoveries in the frontier field of immunology and proposed new academic views. The collaborating team led by Academician Cao Xuetao found that the major histocompatibility complex (MHC) class I molecules have new important non-classical functions, that is, they can suppress non-specific (natural) anti-infective immune responses and inflammatory responses through reverse signaling pathways In the past, it was traditionally believed that MHC class I molecules that participate in a specific immune response after a natural immune response can participate in a non-specific natural immune response earlier than originally thought, and proposed a new mode of natural immune function regulation. Relevant achievements were published in the latest issue of "Nature-Immunology" recently.
This is another systematic and in-depth study of the team following the release of another classic MHC molecule in the Nature-Immunology last April, MHC class II molecules, which can enhance the natural immune response against infection.
According to reports, macrophages and dendritic cells are two specialized antigen-presenting cells, and their expression of various natural immune recognition receptors, including Toll-like receptors (TLR), can recognize and perceive components of pathogenic microorganisms. The immune system recognizes pathogen invasion and then stimulates the natural immune response to clear pathogens and plays a key role.
In order to answer the question of how to avoid excessive activation and cause inflammation damage after TLR triggers innate immune response, at the same time, in order to understand whether MHC class I and II molecules are involved in innate immune response and inflammation regulation, Cao Xuetao and doctoral student Xu Sheng etc. In their research, they found that membrane MHC class I molecules constitutively expressed on the surface of macrophages and dendritic cells can recruit tyrosine kinase Fps and phosphatase SHP-2 through reverse signal transduction to form a signal complex , Feedback-blocking TLR signal transduction, thereby inhibiting innate immunity and inflammation, and protecting mice from sepsis caused by bacterial infection. This study revealed a new mechanism of negative regulation of TLR signal transduction and proved that constitutively expressed MHC class I molecules can suppress natural immune responses and inflammatory responses through reverse signaling.
Experts believe that the discovery provides new ideas for further basic research on natural immune recognition and regulation and the development of related anti-infective and anti-inflammatory drugs.
This subject was jointly completed by the State Key Laboratory of Medical Immunology of the Second Military Medical University, the National Biomedical Analysis Center of the Academy of Military Medical Sciences, and the State Key Laboratory of Medical Molecular Biology of the Chinese Academy of Medical Sciences.
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