RÉSUMÉ
Innate immune system activation is crucial in the inflammatory response, but uncontrolled activation can lead to autoimmune diseases. Cellular exhaustion and senescence are two processes that contribute to innate immune tolerance breakdown. Exhausted immune cells are unable to respond adequately to specific antigens or stimuli, while senescent cells have impaired DNA replication and metabolic changes. These processes can impair immune system function and disrupt homeostasis, leading to the emergence of autoimmunity. However, the influence of innate immune exhaustion and senescence on autoimmune disorders is not well understood. This review aims to describe the current findings on the role of innate immune exhaustion and senescence in autoimmunity, focusing on the cellular and molecular changes involved in each process. Specifically, the article explores the markers and pathways associated with immune exhaustion, such as PD-1 and TIM-3, and senescence, including Β-galactosidase (β-GAL), lamin B1, and p16ink4a, and their impact on autoimmune diseases, namely type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and immune-mediated myopathies. Understanding the mechanisms underlying innate immune exhaustion and senescence in autoimmunity may provide insights for the development of novel therapeutic strategies.
RÉSUMÉ
Objective To explore the effect of immune senescence on lung cancer metastasis and reveal the mechanism of Fuzheng traditional Chinese medicine Jinfukang in the prevention and treatment of the metastasis. Methods A lung metastasis model of Lewis lung cancer cells was established in C57BL/6 mice with different ages (15 months, 6 months, and 2 months). Mice in the 6-month-old group were given Jinfukang intragastrically for 42 days. Pulmonary metastasis was analyzed by in vivo imaging, anatomical microscopic observation, and HE staining. The proportion of memory T cells and NK cells in peripheral blood was detected by flow cytometry. Results The lung metastatic tumor formation rate of 15-month-old and 6-month-old mice was significantly higher than that of 2-month-old mice (all P < 0.05). Abundance of CD4+T cells in peripheral blood was positively correlated with age (2-month-old vs. 6-month-old, P=0.041; 2-month-old vs.15-month-old, P=0.041; 6-month-old vs.15-month-old, P=0.953). The abundance of NK cells was negatively correlated with age (2-month-old vs. 6-month-old, P=0.009; 2-month-old vs.15-month-old, P=0.009; 6-month-old vs. 15-month-old, P=0.574). However, the survival time of mice in the Jinfukang group was longer (P > 0.05) and the level of NK cells in peripheral blood was significantly higher (P=0.029) than those in the normal saline group. Conclusion Immune senescence can promote the metastasis of lung cancer. The prolongation of the survival time of mice administered with Jinfukang may be related to delaying immune senescence and increasing the number of NK cells.
RÉSUMÉ
Immune senescence is a phenomenon in which immune function gradually decreases to dysfunction with the increase of age, and it is a gradual natural degeneration process of the gene-controlled immune system. It is mainly manifested in the weakening of immune recognition and immune response, and the disorder of immune function. The immune dysfunction and immune senescence may also occur to different degree in HIV-1-infected patients and aging people. HIV infection and aging will both lead to immune dysfunction. HIV infection is associated with abnormalities in all major lymphocyte populations, including B cells, which ultimately result in severe exhaustion of several lymphocyte functions and increases susceptibility to secondary and opportunistic infections. Recently, with the increasing trend of the aging of HIV-1-infected/AIDS patients, the elderly have become a high-risk group of HIV infection. Thus, it is of great practical and clinical significance to better understand the pathogenic mechanisms of B-cell abnormalities in HIV disease, compare and analyze the changes of immune system in elderly and young HIV patients, and explore more efficient ways of prevention and treatment of elderly HIV/AIDS patients.