0000000000586045
AUTHOR
Fatma Doener
Impaired Mast Cell-Driven Immune Responses in Mice Lacking the Transcription Factor NFATc2
Abstract The three calcium-dependent factors NFATc1, c2, and c3 are expressed in cells of the immune system and play pivotal roles in modulating cellular activation. With regard to NFATc2, it was reported that NFATc2-deficient mice display increased immune responses in several models for infection and allergy in vivo. This led to the assumption that NFATc2 is involved in the maintenance of immune homeostasis. Using the synthetic TLR7 agonist imiquimod as an adjuvant in epicutaneous peptide immunization, we observed that both the inflammatory reaction and the peptide-specific CTL response are severely impaired in NFATc2-deficient mice. Detailed analyses revealed that early production of proi…
Mast cell-derived mediators promote murine neutrophil effector functions
Mast cells are able to trigger life-saving immune responses in murine models for acute inflammation. In such settings, several lines of evidence indicate that the rapid and protective recruitment of neutrophils initiated by the release of mast cell-derived pro-inflammatory mediators is a key element of innate immunity. Herein, we investigate the impact of mast cells on critical parameters of neutrophil effector function. In the presence of activated murine bone marrow-derived mast cells, neutrophils freshly isolated from bone marrow rapidly lose expression of CD62L and up-regulate CD11b, the latter being partly driven by mast cell-derived TNF and GM-CSF. Mast cells also strongly enhance neu…
Genetic Variation Determines Mast Cell Functions in Experimental Asthma
Abstract Mast cell-deficient mice are a key for investigating the function of mast cells in health and disease. Allergic airway disease induced as a Th2-type immune response in mice is employed as a model to unravel the mechanisms underlying inception and progression of human allergic asthma. Previous work done in mast cell-deficient mouse strains that otherwise typically mount Th1-dominated immune responses revealed contradictory results as to whether mast cells contribute to the development of airway hyperresponsiveness and airway inflammation. However, a major contribution of mast cells was shown using adjuvant-free protocols to achieve sensitization. The identification of a traceable ge…