The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4⁺ T cells.

TRPV1 is a Ca(2+)-permeable channel studied mostly as a pain receptor in sensory neurons. However, its role in other cell types is poorly understood. Here we found that TRPV1 was functionally expressed in CD4(+) T cells, where it acted as a non-store-operated Ca(2+) channel and contributed to T cell antigen receptor (TCR)-induced Ca(2+) influx, TCR signaling and T cell activation. In models of T cell-mediated colitis, TRPV1 promoted colitogenic T cell responses and intestinal inflammation. Furthermore, genetic and pharmacological inhibition of TRPV1 in human CD4(+) T cells recapitulated the phenotype of mouse Trpv1(-/-) CD4(+) T cells. Our findings suggest that inhibition of TRPV1 could represent a new therapeutic strategy for restraining proinflammatory T cell responses.

STAT3: An Anti-Invasive Factor in Colorectal Cancer?

Signal Transducer and Activator of Transcription 3 (STAT3) is activated in a majority of cancers, and promotes tumorigenesis and even metastasis through transcriptional activation of its target genes. Recently, we discovered that STAT3 suppresses epithelial-to-mesenchymal transition (EMT) and thus metastasis in a mouse model of colorectal cancer (CRC), while it did not affect the overall tumor burden. Furthermore, we found that STAT3 in intestinal epithelial cells (IEC) suppresses EMT by regulating stability of an EMT inducer, SNAI-1 (Snail-1). Here, STAT3 functions as an adaptor rather than a transcription factor in the post-translational modification of SNAI-1. In this review, we discuss the unexpected and contradictory role of STAT3 in metastasis of CRC and its clinical implications.

Generalized tetanus in a 4-year old boy presenting with dysphagia and trismus: a case report.

INTRODUCTION: The low incidence of tetanus in developed countries has resulted in a decreased vigilance of this disease. This raises concern, as the prodromal stadium of a generalized tetanus infection may lack the characteristic paroxysmal muscle spasms. Tetanus can rapidly progress into life-threatening muscle spasms accompanied by respiratory insufficiency and/or autonomic dysfunction. This emphasizes the need for early diagnosis and treatment. CASE PRESENTATION: A 4-year-old Caucasian boy presented with a one-week history of general malaise, mild fever, indolence and anorexia. He subsequently developed dysphagia, sialorrhoea, difficulties opening the mouth and eventually dehydration. Due to parental concerns about the boy's refusal of fluids, a pediatrician was consulted. At that time of presentation he showed signs of trismus and muscle rigidity. Together with the lack of immunization and a toe nail infection, this lead to the suspicion of a generalized tetanus infection. After sedation, endotracheal intubation and ventilation, passive immunization and initiation of antimicrobial treatment, he was immediately transferred to a pediatric intensive care unit (PICU) for further treatment. The frequency and severity of paroxysmal muscle spasms increased progressively during his PICU stay, despite high doses of sedatives. Not before two weeks after admittance, extubation and careful weaning off sedatives was achieved. CONCLUSION: Tetanus infection remains a rare but potentially lethal disease in developed countries. As the full scope of classical symptoms may be absent at first presentation, tetanus should always be considered in non-immunized patients with an acute onset of dysphagia and trismus.