Regulatory B Cells - Implications in Autoimmune and Allergic Disorders

B lymphocytes are a major player in the immune system and their best understood effector functions are antibody production, presentation of antigens to T cells and modulation of immune responses via cytokine production. Most B cell functions are considered to amplify immune responses, but it has also been demonstrated that due to production of immunosuppressive cytokines or antibodies, B cells can down-regulate immune responses and have the ability to induce tolerance. These B cells with regulatory capacity (Breg cells) have been shown to suppress effector functions of various target cells including T cells, dendritic cells and macrophages, and can even convert effector T cells into regulatory T cells. The most prominent mechanism of Breg mediated suppression is the release of anti-inflammatory cytokines such as IL-10 and TGF-β. Additional suppression mechanisms via cell-cell contact, involving surface molecules such as program death-1 (PD-1), CD80/CD86 and FasL mediating target cell apoptosis, have been described as well. Most importantly, Breg cells have been implicated in various inflammatory conditions, such as allergic and autoimmune diseases. There is evidence for Breg deficiencies in human SLE patients and various adoptive transfer experiments in mouse models of autoimmune and allergic diseases indicate that Breg cells are capable of suppressing disease development. In this review we endeavour to give an overview of the current knowledge about regulatory B cell immunobiology and their implications in allergic and autoimmune conditions.published_or_final_versio

IL-10-producing regulatory B cells induced by IL-33 (BregIL-33) effectively attenuate mucosal inflammatory responses in the gut

Regulatory B cells (Breg) have attracted increasing attention for their roles in maintaining peripheral tolerance. Interleukin 33 (IL-33) is a recently identified IL-1 family member, which leads a double-life with both pro- and anti-inflammatory properties. We report here that peritoneal injection of IL-33 exacerbated inflammatory bowel disease in IL-10-deficient (IL-10-/-) mice, whereas IL-33-treated IL-10-sufficient (wild type) mice were protected from the disease induction. A phenotypically unconventional subset(s) (CD19+CD25+CD1dhiIgMhiCD5-CD23-Tim-1-) of IL-10 producing Breg-like cells (BregIL-33) was identified responsible for the protection. We demonstrated further that BregIL-33 isolated from these mice could suppress immune effector cell expansion and functions and, upon adoptive transfer, effectively blocked the development of spontaneous colitis in IL-10-/- mice. Our findings indicate an essential protective role, hence therapeutic potential, of BregIL-33 against mucosal inflammatory disorders in thegut. © 2014.link_to_subscribed_fulltex

Priming Dendritic Cells for Th2 Polarization: Lessons Learned from Helminths and Implications for Metabolic Disorders

Cancer Signaling networks and Molecular Therapeutic

Equivalence of complex drug products: advances in and challenges for current regulatory frameworks

Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified

Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor

Host-parasite interactio