Role of Mast Cells and Basophils in IgE Responses and in Allergic Airway Hyperresponsiveness

Abstract

We established a diphtheria toxin (DT)-based conditional deletion system using Il4 enhancer elements previously shown to be specific for IL-4 production in mast cells (MCs) or basophils (Mas-TRECK and Bas-TRECK mice). DT treatment of Bas-TRECK mice resulted in specific deletion of basophils, whereas both MCs and basophils were deleted in Mas-TRECK mice. DT-treated Mas-TRECK mice had impaired passive cutaneous anaphylaxis, IgE-mediated passive systemic anaphylaxis, and IgE-mediated chronic allergic inflammation, whereas DT-treated Bas-TRECK mice had impaired IgE-mediated chronic allergic inflammation. Using these mice, we also sought to tease out the role of MCs and basophils in airway hyperresponsiveness (AHR). Although MC deletion resulted in a slight increase in basal Ag-specific IgE levels and significant increases in basal IgE levels, we found that this deletion markedly impaired the AHR effector phase and was accompanied by decreased histamine levels. By contrast, basophil deletion had no effect on the AHR effector phase or on IgE production induced by systemic OVA immunization. Our results, using these newly established Mas-TRECK and Bas-TRECK models, demonstrated an indispensable role for MCs as effector cells in AHR.

Differences in the Importance of Mast Cells, Basophils, IgE, and IgG versus That of CD4+T Cells and ILC2 Cells in Primary and Secondary Immunity to Strongyloides venezuelensis

“…We used genetic approaches to investigate the relative contributions of MCs and basophils in primary and secondary infections with S. venezuelensis. MC-deficient WBB6F 1 -Kit W/W-v mice exhibited delayed expulsion of S. venezuelensis in primary infections (6,7,11), but such mice have other abnormalities related to their c-kit mutations that may influence the response to this parasite by mechanisms unrelated to their MC deficiency (17,(32)(33)(34)(35).…”

“…1B). Another genetically engineered MC-deficient mouse (with normal c-kit), the MasTRECK (Tg/ϩ) mouse (32), exhibited a 7-day delay in cessation of egg excretion compared to diphtheria toxin (DT)-treated littermate wildtype control (ϩ/ϩ) or phosphate-buffered saline (PBS)-treated MasTRECK mice ( Fig. 1C; also see Fig.…”

“…Beyond a profound MC deficiency, both Hello Kitty mice (36) and, at early times after DT treatment, DT-treated MasTRECK mice (32) have significantly reduced numbers of basophils. We therefore also tested MC-deficient C57BL/6J-Kit W-sh/W-sh mice (37), which have Kit-related MC deficiency but have slightly increased numbers of basophils (37).…”

IgE knock‐in mice suggest a role for high levels of IgE in basophil‐mediated active systemic anaphylaxis

“…The probable reason for this difference is that passive sensitization with monoclonal IgE is less efficient, due to the instability of IgE, compared with a polyclonal IgE antibody response. Recently, Sawaguchi et al showed that in a passive systemic anaphylaxis model, mast cell but not basophil depletion inhibited anaphylaxis [38]. In addition, Ohnmacht et al [40] demonstrated for the Mcpt8Cre-basophil-deficient mouse model that in active systemic anaphylaxis no difference between controls and the basophil-lacking mice exist.…”

Analyzing the Functions of Mast Cells <em>In Vivo</em> Using '<em>Mast Cell Knock-in</em>' Mice

“…If we obtain concordant results in both types of MC-deficient mice, we then proceed to engraftment experiments to ascertain the role of MCs and assess the potential roles of certain MC-derived products. Finally, it should be noted that several strains allowing inducible depletion of MCs or Cre recombinase-mediated deletion of "floxed" genes in MCs have also been recently described 25,49,61 . These strains have been reviewed in detail elsewhere 9,10,13 and represent promising alternative -or complementary -approaches to study MC functions in vivo.…”