The immune system is highly complicated. In addition to the traditional classification of immune cell types, the strength of immune cell functions and the states of activation, inhibition, and exhaustion will have a great impact on immune functions. These effects are not only related to infectious diseases and autoimmune diseases, but also to the immune reactions after transplantation. High-throughput single-cell sequencing can not only profile the types and status of immune cells, but also analyze the complex interaction between the activation or inhibition of cells, providing a powerful tool for immunological research.
The immune system is composed of many types of cells that work together to sense and respond to external stimuli and physiological changes to monitor and maintain health. The scRNA-seq technology can analyze the innate and adaptive immune responses, and facilitate next-generation therapies for inflammation, autoimmunity, and cancer.
The immune system functions as immune surveillance, defense, and regulation. Theses functions require a complex network of interactions. The scRNA-seq technology has demonstrated the ability to simultaneously detect multiple functions of the immune response. For example, researchers used scRNA-seq technology to provide a cellular map of the peripheral immune response to severe COVID-19, and deciphered the remodeling of the phenotype of peripheral immune cells in COVID-19, including the genetic characteristics of heterogeneous interferon stimulation and Down-regulation of HLA class II genes and so on.
When exposed to various infectious pathogens, immune cells will participate in various important biological processes, such as pathogen recognition, killing, and antigen presentation. The scRNA-seq technology can identify new immune cell subgroups and analyze their molecular characteristics, dynamics and functions during the infection process, thereby improving our understanding of infectious disease mechanisms and subsequent treatment strategies. For example, researchers used scRNA-seq technology to identify three subpopulations of lung macrophages from tuberculosis patients and found that they have different origins or adapt to different microenvironments in tuberculosis patients.
When the dynamic balance of the immune system is disrupted and normal functions are disturbed, autoimmune diseases might occur. scRNA-seq can explore the mechanism of autoimmune diseases from the single-cell level and find new therapeutic targets. For example, some researchers have used scRNA-seq technology to discover that the chemokine receptors CXCR4 and CX3CR1 are frequently expressed in patients with lupus nephritis, suggesting that they may be potential therapeutic targets.
The immune system plays a vital role in transplant rejection and post-transplant infection, but the underlying mechanisms have not been fully elucidated. The scRNA-seq technology provides a tool for analyzing the complex immune regulatory network during transplant rejection and post-transplant infection. In a case study, researchers used scRNA-seq technology to find that endothelial cells formed three different subpopulations: resting cells and two activated endothelial cell populations. A group of activated endothelial cells express Fc receptor pathway activation and Ig internalization genes, consistent with the pathological diagnosis of antibody-mediated rejection.