Immunization of BALB/c mice with pigeon IgY induces the production of anti-IgG autoantibodies

The breakdown of immunological tolerance due to the activation of autoreactive B and T cells triggers physiopathological processes. An example of such conditions is the production of IgG autoantibodies specific for the Fc portion of IgG (anti-Fcγ IgG). Previous reports have shown that patients with pigeon-related hypersensitivity pneumonitis exhibit an increase in the serum levels of anti-Fcγ IgG. There is no in vivo model for the study of this condition and the immunological mechanisms of tolerance breakdown associated with sensitization by pigeon antigens are still unknown. In this work, we show that the repeated immunization of BALB/c mice with pigeon IgY during 16-weeks induces the production of anti-Fcγ IgG and keeps their high levels for seven weeks. The late appearance of anti-Fcγ IgG autoantibodies in the plasma is similar to what has been reported in other experimental autoimmune models. With the occurrence of anti-Fcγ IgG, there is a reduction in the proportion of Foxp3 + cells (regulatory T cells, Tregs) within the population of splenic CD4 + CD25 + T cells. Thus, our data showed that the immunization of BALB/c mice with IgY promotes the production of anti-Fcγ IgG along with a decrease in Tregs in the spleen. We propose that immunization of mice with pigeon antigens, like IgY can provide a model to study the immunological mechanisms involved in the development of pigeon-related hypersensitivity pneumonitis

The Scribble Complex PDZ Proteins in Immune Cell Polarities

hScrib and hDlg belong to the PDZ family of proteins. Since the identification of these highly phylogenetically conserved scaffolds, an increasing amount of experiments has elucidated the roles of hScrib and hDlg in a variety of cell functions. Remarkably, their participation during the establishment of polarity in epithelial cells is well documented. Although the role of both proteins in the immune system is scantly known, it has become a growing field of investigation. Here, we summarize the interactions and functions of hScrib and hDlg1, which participate in diverse functions involving cell polarization in immune cells, and discuss their relevance in the immune cell biology. The fundamental role of hScrib and hDlg1 during the establishment of the immunological synapse, hence T cell activation, and the recently described role of hScrib in reactive oxygen species production in macrophages and of hDlg1 in cytokine production by dendritic cells highlight the importance of both proteins in immune cell biology. The expression of these proteins in other leukocytes can be anticipated and needs to be confirmed. Due to their multiple interaction domains, there is a wide range of possible interactions of hScrib and hDlg1 that remains to be explored in the immune system