Basophils and mast cells play critical roles in host defense against pathogens and allergic disorders. However, the molecular mechanism by which these cells are generated is not completely understood. Here we demonstrate that interferon regulatory factor-8 (IRF8), a transcription factor essential for the development of several myeloid lineages, also regulates basophil and mast cell development....

Previous studies have shown that mouse bone marrow cells can produce mast cells when stimulated in vitro by stem cell factor (SCF) and interleukin-3 (IL-3). Experiments to define the marrow cells able to generate mast cells showed that the most active subpopulations were the Kit(+) Sca1(-) progenitor cell fraction and the more ancestral Kit(+) Sca1(+) blast colony-forming cell fraction. In clon...

Type 2 inflammation underlies allergic diseases such as atopic dermatitis, which is characterized by the accumulation of basophils and group 2 innate lymphoid cells (ILC2s) in inflamed skin lesions. Although murine studies have demonstrated that cutaneous basophil and ILC2 responses are dependent on thymic stromal lymphopoietin, whether these cell populations interact to regulate the developmen...

Recent work has established important roles for basophils in regulating immune responses. To exert their biological functions, basophils need to be expanded to critical numbers. However, the mechanisms underlying basophil expansion remain unclear. In this study, we established that IL-3 played an important role in the rapid and specific expansion of basophils. We found that the IL-3 complex (IL...

Hookworms infect several hundred million people worldwide, causing malnutrition, anemia, and growth retardation. Infections generally result in a strong type 2 immune response, but the effector mechanisms that mediate worm expulsion remain poorly characterized. In this study, we determined the role of mast cells and basophils in protective immunity against the murine hookworm, Nippostrongylus B...

Basophils are rare, circulating leukocytes derived from hematopoietic CD34+ progenitors. The identification of cytokines promoting their development in vitro has led to substantial advances in understanding their differentiation process. An important role could be assigned to interleukin-3 (IL-3), which supports the maturation of hematopoietic progenitors into basophils in vitro and in vivo. In...

Anaphylactic reactions in the peri-operative period are often serious and potentially life-threatening conditions, involving multiple organ systems in which the clinical manifestations are the consequence of the release of preformed mediators from mast cells and basophils. Anaphylaxis is an immune mediated type I allergic reaction following the massive release of mediators from mast cells and b...

Vertebrate immunity has evolved a modular architecture in response to perturbations. Allergic inflammation represents such a module, with signature features of antigen-specific IgE and tissue eosinophilia, although the cellular and molecular circuitry coupling these responses remains unclear. Here, we use genetic and imaging approaches in models of IgE-dependent eosinophilic dermatitis to demon...