Jueves 21 de Febrero de 2008; 12:12hrs.

IL-21 regulates experimental colitis by modulating the balance between Treg and Th17 cells

 

• Massimo C. Fantini, Agelamaria Rizzo, Daniele Fina et al. European Journal of Immunology 2007; 37: 3155-3163
  
  
• Regulatory T (Treg) cells play a key role in the maintenance of the immune system homeostasis. Treg cells can be generated in the periphery under control of TGF-, a cytokine involved in the negative control of the immune system. However, TGF- cooperates with IL-6 in the generation of Th17 cells, a novel class of effector cells involved in numerous inflammatory diseases, including colitis. Therefore, TGF- emerges as a mediator of both anti-inflammatory and pro-inflammatory processes, depending on the local cytokine milieu. Here we demonstrate that IL-21, a type-1 cytokine produced by T cells and involved in the pathogenesis of immune-mediated diseases, prevents the TGF--dependent expression of FoxP3, the master regulator of Treg cell commitment, and the induction of suppressive capacity in naive CD4+ T cells, while promoting the differentiation of Th17 cells. In vivo, CD4+ naive T cells activated in the presence of TGF- and IL-21 failed to suppress colitis while inducing an inflammatory response characterized by high levels of IL-17 and RORt, the transcription factor expressed by Th17 cells. Therefore, IL-21 emerges as a key modulator of TGF- signaling, leading to the reciprocal differentiation of Treg and Th17 cells......Más...

 

Lunes 18 de Febrero de 2008; 10:05 hrs.

Mucosal Damage and Neutropenia Are Required for Candida albicans Dissemination

 

• Koh AY, Köhler JR, Coggshall KT, Van Rooijen N, Pier GB PLoS Pathogens Vol. 4, No. 2, e35 doi:10.1371/journal.ppat.0040035
• Candida albicans fungemia in cancer patients is thought to develop from initial gastrointestinal (GI) colonization with subsequent translocation into the bloodstream after administration of chemotherapy. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but we have hypothesized that both neutropenia and GI mucosal damage are critical for allowing widespread invasive C. albicans disease. We investigated these parameters in a mouse model of C. albicans GI colonization that led to systemic spread after administration of immunosuppression and mucosal damage. After depleting resident GI intestinal flora with antibiotic treatment and achieving stable GI colonization levels of C. albicans, it was determined that systemic chemotherapy with cyclophosphamide led to 100% mortality, whereas selective neutrophil depletion, macrophage depletion, lymphopenia or GI mucosal disruption alone resulted in no mortality. Selective neutrophil depletion combined with GI mucosal disruption led to disseminated fungal infection and 100% mortality ensued. GI translocation and dissemination by C. albicans was also dependent on the organism's ability to transform from the yeast to the hyphal form. This mouse model of GI colonization and fungemia is useful for studying factors of innate host immunity needed to prevent invasive C. albicans disease as well as identifying virulence factors that are necessary for fungal GI colonization and dissemination. The model may also prove valuable for evaluating therapies to control C. albicans infections.....Más.