It’s Time to Bring Dendritic Cell Therapy to Type 1 Diabetes

作者：Rémi J. Creusot, Nick Giannoukakis, Massimo Trucco, Michael Clare‐Salzler, C. Garrison Fathman · 发表于：Diabetes · 年份：2013 · DOI：10.2337/db13-0886 · 被引用次数：51 · 研究领域：Diabetes and associated disorders、Immune Cell Function and Interaction、T-cell and B-cell Immunology

Type 1 diabetes (T1D) is an autoimmune disease that results from a deficient induction or maintenance of tolerance to islet β-cell antigens, allowing the eventual T-cell–mediated destruction of insulin-producing β-cells within the pancreatic islets (1). Under homeostatic conditions, immune tolerance is established by various subsets of antigen-presenting cells (APCs) with tolerance-inducing/maintaining (tolerogenic) functions and reinforced by other cells with suppressor and immunomodulatory properties. T-cell tolerance manifests itself through elimination (deletion), inactivation (anergy), or suppression of self-reactive T cells (Fig. 1 A ). These functions may be performed by a variety of tolerogenic APCs (Table 1), some of which have the ability to induce/boost regulatory T cells (Tregs) and/or B cells (Bregs). Genetic and environmental factors that vary among different individuals contribute to the development of T1D, in part by impacting mechanisms of tolerance (Fig. 1 B ). Therefore, a major goal for the prevention and/or reversal of T1D is to restore effective and durable tolerance to either prevent further destruction of remaining islet β-cells, help islet β-cell regeneration, or protect islet transplants and obviate the use of nonspecific immunosuppressive drugs. The approach reviewed here consists of developing a personalized therapy using the patient’s own cells manipulated to perform as tolerogenic APCs (Fig. 1 C ). In this review, we will explain why dendritic ce...