Understand tolerogenic dendritic cells

In this issue of Blood, Bros and colleagues report thoroughly how glucocorticoid (GC) treatment of a murine dendritic cell (DC) line during maturation induces a stable dendritic cell state with tolerogenic characteristics, similar to that described with GC-treated bone marrow–derived dendritic cells.

Although the morphology of glucocorticoid (GC)–treated dendritic cells (DCs) is similar to conventionally matured DCs, they exert poor allogeneic and syngeneic T-cell stimulatory capacity and induce anergic T cells with inhibitory function. Of interest, despite the suppressed expression of costimulatory molecules in GC-treated DCs, the mRNA levels were comparable with conventionally matured DCs. So far, several studies showed impaired maturation, migration, and T-cell stimulatory capacity of GC-treated murine DC lines^1,2  and human myeloid DCs.^3,4  In contrast to these previous studies, Bros and colleagues extensively characterized the immunologic phenotypes, of their stable and tolerogenic DC line. Particularly, 2 aspects are of interest in this paper: first, the GCs that are used to induce tolerogenicity and second, the state of tolerogenicity itself. Concerning the first aspect, GCs (cortisol in humans) are widely applied as immunosuppressive and anti-inflammatory agents to treat autoimmune or allergic disease and to prevent graft rejection. They play a crucial role in inducing tolerance to environmental and self-antigens and undermine primary and memory CD8⁺ cytotoxic T-lymphocyte responses. Besides, GCs are also commonly used in the treatment of B-cell malignancies based on their potential to directly induce apoptosis. Concerning the second aspect, the properties of a tolerogenic state are not understood in detail and are certainly complex. An abundantly available cell line with stable characteristics is a valuable tool to more deeply investigate the GCs and the tolerogenic state in general on dendritic cells. It paves the way to perform detailed studies on the diverse functional aspects of tolerogenicity, including antigen presentation, migratory function, cytokine secretion, and costimulatory capacity. This knowledge will provide a rationale for intervention, for example conserving one DC function while suppressing another, such as preserving antitumor effects of GCs against B-cell malignancies, while inhibiting the negative impact on antigen presentation and T-cell stimulatory capacity of DCs.

Physiologically GCs are hormones that are naturally released via the hypothalamic-pituitary-adrenal axis in response to certain stimuli, such as stress. Therefore, their regulatory function extends beyond the clinical setting to daily life.