The binding of immunoglobulin E (IgE) to high affinity IgE receptors (FcεRI) expressed on the surface of mast cells primes these cells to secrete, upon subsequent exposure to specific antigen, a panel of proinflammatory mediators, which includes cytokines that can also have immunoregulatory activities. This IgE- and antigen-specific mast cell activation and mediator production is thought to be critical to the pathogenesis of allergic disorders, such as anaphylaxis and asthma, and also contributes to host defense against parasites. We now report that exposure to IgE results in a striking (up to 32-fold) upregulation of surface expression of FcεRI on mouse mast cells in vitro or in vivo. Moreover, baseline levels of FcεRI expression on peritoneal mast cells from genetically IgE-deficient (IgE −/−) mice are dramatically reduced (by ∼83%) compared with those on cells from the corresponding normal mice. In vitro studies indicate that the IgE-dependent upregulation of mouse mast cell FcεRI expression has two components: an early cycloheximide-insensitive phase, followed by a later and more sustained component that is highly sensitive to inhibition by cycloheximide. In turn, IgE-dependent upregulation of FcεRI expression significantly enhances the ability of mouse mast cells to release serotonin, interleukin-6 (IL-6), and IL-4 in response to challenge with IgE and specific antigen. The demonstration that IgE-dependent enhancement of mast cell FcεRI expression permits mast cells to respond to antigen challenge with increased production of proinflammatory and immunoregulatory mediators provides new insights into both the pathogenesis of allergic diseases and the regulation of protective host responses to parasites.

We attempted to elicit active anaphylaxis to ovalbumin, or passive IgE-or IgG 1 -dependent anaphylaxis, in mice lacking either the Fc ⑀ RI ␣ chain or the FcR ␥ chain common to

Contact sensitivity responses require both effective immune sensitization following cutaneous exposure to chemical haptens and antigen-specific elicitation of inflammation upon subsequent hapten challenge. We report that antigen-independent effects of IgE antibodies can promote immune sensitization to haptens in the skin. Contact sensitivity was markedly impaired in IgE(-/-) mice but was restored by either transfer of sensitized cells from wild-type mice or administration of hapten-irrelevant IgE before sensitization. Moreover, IgE(-/-) mice exhibited impairment in the reduction of dendritic cell numbers in the epidermis after hapten exposure. Monomeric IgE has been reported to influence mast cell function. We observed diminished contact sensitivity in mice lacking FcepsilonRI or mast cells, and mRNA for several mast cell-associated genes was reduced in IgE(-/-) versus wild-type skin after hapten exposure. We speculate that levels of IgE normally present in mice favor immune sensitization via antigen-independent but FcepsilonRI-dependent effects on mast cells.

In mouse mast cells, both Fc ⑀ RI and Fc ␥ RIII are ␣␤␥ 2 tetrameric complexes in which different ␣ chains confer IgE or IgG ligand recognition while the signaling FcR ␤ and ␥ chains are identical. We used primarily noninvasive techniques (changes in body temperature, dye extravasation) to assess systemic anaphylactic responses in nonanesthetized wild-type, Fc ⑀ RI ␣ chain Ϫ / Ϫ and FcR ␥ chain Ϫ / Ϫ mice. We confirm that systemic anaphylaxis in mice can be mediated largely through IgG 1 and Fc ␥ RIII and we provide direct evidence that these responses reflect activation of Fc ␥ RIII rather than Fc ␥ RI.

This retrospective study showed that cirrhosis at diagnosis of AIH and abnormal ALT at final observation were independently associated with HCC development. It is important to pay attention to the presence of cirrhosis at diagnosis of AIH and to normalize ALT.