Role of Dendritic Cells in Inflammation and Loss of Tolerance in the Elderly

Abstract

Dendritic cells (DCs) play an important role in advancing age-associated progressive decline in adaptive immune responses, loss of tolerance, and development of chronic inflammation. In aged humans, DCs secrete increased levels of pro-inflammatory cytokines and decreased levels of anti-inflammatory and immune-regulatory cytokines. This may contribute to both chronic inflammation and loss of tolerance in aging. Aged DCs also display increased immune response against self-antigens contributing further to both inflammation and loss of tolerance. The secretion of innate protective cytokines such as type I and III interferons is decreased, and the function of DCs in airway remodeling and inflammation in aged is also compromised. Furthermore, the capacity of DCs to prime T cell responses also seems to be affected. Collectively, these changes in DC functions contribute to the immune dysfunction and inflammation in the elderly. This review only focuses on age-associated changes in DC function in humans.

Keywords: aging; dendritic cells; inflammation; mucosa; tolerance.

Figure 1

Altered functions of dendritic cells (DCs) from elderly contribute to chronic inflammation: DCs from elderly display an enhanced basal level of activation, which increases their reactivity to self-antigens, affects the function of epithelial barrier, and results in erosion of peripheral and mucosal tolerance at homeostasis. After activation with pathogens, DCs from elderly secrete enhanced levels of pro-inflammatory cytokines, which are not regulated as the secretion of anti-inflammatory cytokine IL-10 is impaired. This also contributes to inflammation. In addition, secretion of protective cytokines such as the IFN-α and IFN-λ is also decreased resulting in a decrease in the ability of elderly to fight infections. Figure depicts the differences in the response of DCs from aged and young subjects at homeostasis and after activation.