Background Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition... Show moreBackground Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated whether school-aged children with and without FLG mutations have differences in T- and B-cell subsets.Methods This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X, and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg), and CD27(+) and CD27(-) memory B cells. Subset analysis was performed in 358 non-AD and 102 AD cases, assessed by parental questionnaires.Results FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children in the general and non-AD population. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg, or memory B-cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cell subsets.Conclusions School-aged children of a general population with FLG mutations have higher Th22 cell numbers, which reflects the immunological response to the skin barrier dysfunction. FLG mutations did not otherwise affect the composition of the adaptive immunity in this general pediatric population. Show less
This thesis describes six studies which characterized tumor-infiltrating leukocytes (TIL) in colorectal cancer. TIL have shown to be of importance in the natural anti-tumor immunity of cancer... Show moreThis thesis describes six studies which characterized tumor-infiltrating leukocytes (TIL) in colorectal cancer. TIL have shown to be of importance in the natural anti-tumor immunity of cancer patients. Chapter 1 gives an introductory overview of tumor immunology, TIL and colorectal cancer. In chapter 2 we describe the presence, location, and phenotype of tumor-infiltrating dendritic cells in colorectal cancer. With special attention to their association with other tumor-infiltrating immune cells, i.e. lymphocytes. Chapter 3 elaborates further on the role of tumor-infiltrating DC by evaluating whether there is an association between the presence and maturation status of tumor-infiltrating DC, T lymphocytes and clinical prognosis in patients with colorectal cancer. In chapter 4 NK cell infiltration in colorectal cancer is studied in relationship with loss of tumor MHC class I expression. In chapter 5 TIL were characterized in a case-control design, with tumors showing complete absence or normal expression of HLA class I. We further characterized TIL in a group of colorectal tumors displaying systemic P53 reactivity in chapter 6. Chapter 7 describes the technique of the multi-color immunohistochemical analysis, which we used to characterize the phenotype of TIL in the two preceding chapters. Chapter 8 Summary and Discussion. Show less
