The group consists of two technicians, two graduated scientists and a variable number of project and graduate students. The focus of interest and consequently the competence profile of the group are the regulation of immune responses. The technology used spans from molecular biology to in vivo experiments.
Current projects in brief
Transcriptional regulation by SPI-C and IKAROS
The transcription factors SPI-C and IKAROS are temporally expressed during B cell differentiation. In this project we aim to understand how these two transcription factors interact in the control of gene expression during B cell differentiation. We also try to determine which are the target genes of SPI-C and in what other cell populations this transcription factor is expressed. Furthermore, we aim at establishing a knock-out mouse model where the SPI-C gene has been inactivated.
Study of J-chain knock-out mice (J-/- mice)
We have established a mouse model where the J-chain locus has been inactivated. Besides the expected phenotype of destroying the formation of dimeric IgA and pentameric IgM we have discovered that these animals have an immunomodulatory phenotype. As a consequence tolerance cannot be induced in these animals and they are hyporesponsive in a model of autoimmune disease (MOG-EAE). Furthermore, we could show that J-/- mice had an altered distribution of dendritic cell (DC) populations. Also, a subpopulation of DC could be shown to express J-chain. In ongoing studies we are characterising the biological activity of this DC subpopulation using transfer experiments in vivo and various in vitro techniques.
Study of tumour-induced immune suppression
As a cancer disease develops the immune system eventually becomes hyporesponsive. At first this is a local phenomenon where the immune system fails to detect the growing tumour as foreign and a target for immune attack. At later stages of malignant disease the immune suppressions tends to become global and the individual becomes more sensitive to opportunistic infections and other immunological challenges. We have established a model for prostate cancer, TRAMP mice, in which we will study the establishment of immune suppression both locally and systemically as the disease develops. This will be made by analysing in detail various immune parameters at various stages of tumour development.
Analysis of the interphase between malignant and inflammatory disease
As pointed out above, immune suppression is commonly seen in association with malignant disease. The mirror image of this state is seen in connection with autoimmune/inflammatory disease where the immune system breaks tolerance and mounts immune responses to the body’s own structures. A number of different genetical changes have been defined that interferes with autoimmune disease. We will analyse whether these genetic loci also affects tumour development and growth by breeding TRAMP mice onto various genetic back-grounds with defined autoimmune susceptibility and study the effect of on tumour growth.