Indoleamine 2, 3-dioxygenase (IDO) is the first and rate limiting catabolic enzyme in the degradation pathway of the essential amino acid tryptophan. By cleaving the aromatic indole ring of tryptophan, IDO initiates the production of a variety of tryptophan degradation products called “kynurenines” that are known to exert important immuno-regulatory functions. Because tryptophan must be supplied in the diet, regulation of tryptophan catabolism may exert profound effects by activating or inhibiting metabolism and immune responses. Important for survival, the regulation of IDO biosynthesis and its activity in cells of the immune system can critically alter their responses to immunological insults, such as infection, autoimmunity and cancer. In this review, we assess how IDO-mediated catabolism of tryptophan can modulate the immune system to arrest inflammation, suppress immunity to cancer and inhibit allergy, autoimmunity and the rejection of transplanted tissues. Finally, we examine how vaccines may enhance immune suppression of autoimmunity through the upregulation of IDO biosynthesis in human dendritic cells.

Dendritic cells (DCs) are considered the dominant antigen presenting cells (APC) in humans and are largely responsible for initiation and guidance of innate and adaptive immune responses involved in maintenance of immunological homeostasis. Immature dendritic cells (iDCs), phagocytize pathogens and toxic proteins and degrade them into small fragments in endosomal vesicles for presentation to naïve cognate T cells (Th0). In addition to stimulation of immunity, DCs are responsible for the induction and maintenance of immune tolerance towards self-antigens. Dendritic cell maturation is initiated when they cease taking up antigens and with the help of several chemokines migrate from the periphery to adjacent lymph nodes or the spleen where during continued maturation they present stored antigens on surface MHCII receptor molecules to the T cell receptor (Tcr) of cognate naive T helper (Th0) cells. During antigen presentation, the DCs upregulate co-stimulatory factor CD86, CD80, CD83, and CD40 molecule biosynthesis on their plasma membrane. The activated DC CD86 and CD80 costimulatory factor molecules bind cognate CD28 receptors on the Th0 cell membrane and secrete pro-inflammatory (IL-12) or anti-inflammatory (IL-10) cytokines that direct T cell differentiation and proliferation into pro- or anti-inflammatory T cell subsets. However, the details of this process remain incomplete. In this review we describe the process of DC maturation in detail and what is known concerning the role of DC maturation in the onset and prevention of Type 1 diabetes tissue specific autoimmunity.

To ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. Being imperfect pathogens, organisms synthesizing multi-subunit AB toxins are responsible for the mortality of millions of people and animals annually. Vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. In response to the debilitating effects of AB toxins on epithelial cells of the digestive mucosa, mechanisms underlying toxin immunomodulation of immune responses have become the focus of increasing experimentation. The results of these studies reveal that AB toxins may have a beneficial application as adjuvants for the enhancement of immune protection against infection and autoimmunity. Here, we examine similarities and differences in the structure and function of bacterial and plant AB toxins that underlie their toxicity and their exceptional properties as immunomodulators for stimulating immune responses against infectious disease and for immune suppression of organ-specific autoimmunity.

In this review, we explore the role of dendritic cell subsets in the development of tissue-specific autoimmune diseases. From the increasing list of dendritic cell subclasses, it is becoming clear that we are only at the beginning of understanding the role of these antigen presenting cells in mediating autoimmunity. Emerging research areas for the study of dendritic cell involvement in the onset and inhibition of tissue-specific autoimmunity are presented. Further, we compare tissue specific to systemic autoimmunity to demonstrate how development of dendritic cell-based therapies may be broadly applicable to both classes of autoimmunity. Continued development of these research areas will lead us closer to clinical assessment of novel immunosuppressive therapy for the reversal and prevention of tissue-specific autoimmunity. Through description of dendritic cell functions in the modulation of tissue-specific autoimmunity, we hope to stimulate a greater appreciation and understanding of the role dendritic cells play in the development and treatment of autoimmunity.

Transgenic chloroplasts are potential bioreactors for recombinant protein production, especially for achievement of high levels of protein expression and proper folding. Production of therapeutic proteins in leaves provides transgene containment by elimination of reproductive structures. Therefore, in this study, human Insulin like Growth Factor-1 is expressed in transgenic chloroplasts for evaluation of structural identity and function.