Both exogenous and endogenous interleukin-10 affects the maturation of bone-marrow-derived dendritic cells in vitro and strongly influences T-cell priming in vivo

In order to avoid autoimmunity and excessive tissue destruction, the action of certain immunoinhibitory substances are very important for negative regulation of the immune system. Interleukin-10 (IL-10) is an important immunoregulatory cytokine which is thought to negatively affect both T cells and antigen-presenting cells in vivo. Adoptive transfer of IL-10-treated bone-marrow-derived dendritic cells (BMDCs) may be one therapeutic avenue to inhibit autoimmunity. In this study we present a comprehensive analysis of the effects of IL-10 on murine BMDC. We demonstrate that IL-10 can prevent BMDC maturation, as measured by both cytokine production and T-cell priming capacity in vitro. Furthermore, we show that IL-10 can inhibit DC maturation induced by strong stimulatory signals such as lipopolysaccharide or a mixture of cytokines (interferon-γ, tumour necrosis factor-α, IL-4). Interestingly, maturation of both T helper 1- and T helper 2-inducing DCs, characterized by the induction of high levels of interferon-γ and IL-4-production by responding T cells, respectively, was inhibited by IL-10 in vitro. Finally, our data suggest that both endogenous and exogenous IL-10 affect the T-cell stimulatory capacity of BMDCs after injection of in vitro-treated BMDCs into naïve mice. These data both support existing data as well as point towards a new understanding of the many aspects of IL-10-mediated immunosuppression

hTERT expression in colorectal adenocarcinoma: correlations with p21, p53 expressions and clinicopathological features

Background: The clinicopathological roles and relationships of hTERT, p21 and p53 proteins have not been studied in depth in colorectal cancer. The aim of the present study is to investigate the clinicopathological roles of expression of hTERT protein expression and its relationship with the expression of p21 and p53 proteins in a large cohort of patients with colorectal adenocarcinoma.\ud Materials and methods: Expressions of hTERT, p21 and p53 proteins were investigated in 188 patients with colorectal adenocarcinomas by immunohistochemistry. The findings were correlated with the clinicopathological features and survival data of colorectal adenocarcinomas.\ud Results hTERT, p53 and p21 proteins were detected in 63%, 100% and 62% of the patients with colorectal carcinoma. High level of hTERT protein expression was noted in patients with metastases (p = 0.038) and in patients with rectal cancer (p  = 0.046). Loss or low level of p21 protein was often noted in non-mucinous colorectal adenocarcinoma when compared with mucinous adenocarcinoma (p = 0.001). Furthermore, p53 expression was more frequently noted in non-mucinous adenocarcinoma (p = 0.001). The level of expression of p21 protein was positively correlated with expression of level of hTERT protein (p = 0.00001). The survival of the patients was related to staging (p = 0.001) and p53 protein expression (p = 0.038) of the tumours.\ud Conclusions: hTERT protein expression is an indicator of the biological aggressiveness of the cancer. The level of expression of the protein was also related to the distal location and level of p21 expression of the tumours

Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells

The control of damaging inflammation by the mucosal immune system in response to commensal and harmful ingested bacteria is unknown. Here we show epithelial cells conditioned mucosal dendritic cells through the constitutive release of thymic stromal lymphopoietin and other mediators, resulting in the induction of 'noninflammatory' dendritic cells. Epithelial cell-conditioned dendritic cells released interleukins 10 and 6 but not interleukin 12, and they promoted the polarization of T cells toward a 'classical' noninflammatory T helper type 2 response, even after exposure to a T helper type 1-inducing pathogen. This control of immune responses seemed to be lost in patients with Crohn disease. Thus, the intimate interplay between intestinal epithelial cells and dendritic cells may help to maintain gut immune homeostasis