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Role of Plasmacytoid Dendritic Cells in Type 1 Diabetes: Friend or Foe?

American Diabetes Association
Publication Date
DOI: 10.2337/db08-1341
  • Commentaries
  • Medicine


Role of Plasmacytoid Dendritic Cells in Type 1 Diabetes: Friend or Foe? Roland Tisch and Bo Wang Type 1 diabetes is characterized by T-cell–medi-ated destruction of insulin-producing �-cells.Progression of �-cell autoimmunity is simplisti-cally viewed as a functional imbalance favoring the development of �-cell–specific pathogenic type 1 ver- sus immunoregulatory T-cells (Tregs) (1,2). The latter consist of a number of distinct subsets with varying functions that can prevent differentiation or function of type 1 T-cells (3). It is unclear how this functional balance between pathogenic T-cells and Tregs goes awry, leading to massive �-cell destruction, or is maintained in at-risk individuals who remain diabetes free. In this issue of Diabetes, Peakman and colleagues (4) investigate den- dritic cells in diabetic patients and provide suggestive evidence for a new player in regulating �-cell–specific T-cell reactivity. Dendritic cells are a heterogeneous group of innate effectors that serve two general functions in controlling T-cell immunity. The first is to process and present anti- gens to T-cells, which is essential for T-cell activation and expansion. Second, dendritic cells secrete cytokines that condition the extracellular milieu and determine the na- ture of the T-cell response. Although much attention has been focused on the capacity of dendritic cells to initiate proinflammatory responses to microbial pathogens, it is clear that dendritic cells serve an important role in estab- lishing and maintaining tolerance to self-antigens (5). These opposing functions are governed by the maturation status and types of cytokines secreted by dendritic cells (6). For instance, infectious microbes in contact with immature dendritic cells promote maturation, which is characterized by the following: 1) an increased capacity to present antigens and stimulate T-cells and 2) secretion of proinflammatory cytokines, which promote differentiation of type 1 T-cells that efficiently clear the infect

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