CD4+ T Cell-Specific Deletion of IL-4 Receptor α Prevents Ovalbumin-Induced Anaphylaxis by an IFN-γ-Dependent Mechanism

Nieuwenhuizen, Natalie E.; Herbert, De’Broski R.; Lopata, Andreas L.; Brombacher, Frank

doi:10.4049/jimmunol.179.5.2758

Cited by 23 publications

(15 citation statements)

References 49 publications

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“…25 Our observation confirmed that mast cells in human colonic tissue express Fc␥RI, but we did not detect the other two types of Fc␥R in colonic mucosa. The differences between those studies and our observation can be local microenvironmentdependent.…”

Section: Discussionsupporting

confidence: 79%

Fc Gamma Receptor Signaling in Mast Cells Links Microbial Stimulation to Mucosal Immune Inflammation in the Intestine

Chen

Feng

Zheng

et al. 2008

The American Journal of Pathology

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Microbes and microbial products are closely associated with the pathogenesis of inflammatory bowel disease (IBD); however, the mechanisms behind this connection remain unclear. It has been previously reported that flagellin-specific antibodies are increased in IBD patient sera. As mastocytosis is one of the pathological features of IBD, we hypothesized that flagellin-specific immune responses might activate mast cells that then contribute to the initiation and maintenance of intestinal inflammation. Thirtytwo colonic biopsy samples were collected from IBD patients. A flagellin/flagellin-specific IgG/Fc gamma receptor I complex was identified on biopsied mast cells using both immunohistochemistry and co-immunoprecipitation experiments; this complex was shown to co-localize on the surfaces of mast cells in the colonic mucosa of patients with IBD. In addition, an ex vivo study showed flagellin-IgG was able to bind to human mast cells. These cells were found to be sensitized to flagellin-specific IgG; re-exposure to

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Section: Discussionsupporting

confidence: 79%

Fc Gamma Receptor Signaling in Mast Cells Links Microbial Stimulation to Mucosal Immune Inflammation in the Intestine

Chen

Feng

Zheng

et al. 2008

The American Journal of Pathology

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“…Control animals received PBS. For induction of endogenous OVA-specific T H 2 cells, DO11.10 mice were sensitized as previously described 19 and challenged with OVA protein, followed by Pam2 injection. Ear thickness was measured with a micrometer (Kroeplin, Schl€ uchtern, Germany) and expressed as a change in ear thickness after treatment.…”

Section: Ovalbumin Sensitization and Adoptive T-cell Transfermentioning

confidence: 99%

Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4–mediated suppression of IL-10

Kaesler

Volz

Skabytska

et al. 2014

Journal of Allergy and Clinical Immunology

101

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“…Infection of these mice with Leishmania major indicated that non-IL-4-responsive CD4 ϩ T cells can launch aspects of a TH2 response (30). Additionally, in ovalbumin-induced anaphylaxis (a TH2-associated pathology) T-cell TH2 cytokine secretion appears to be unaffected by IL-4R␣ CD4 ϩ T-cell expression (28). Together, these findings demonstrate that IL-4R␣ expression on CD4 ϩ T cells is not essential for generation of a TH2 immune response.…”

mentioning

confidence: 99%

Interleukin-4-Promoted T Helper 2 Responses EnhanceNippostrongylus brasiliensis-Induced Pulmonary Pathology

et al. 2008

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The role of CD4 ؉ T-cell interleukin-4 (IL-4) receptor alpha (IL-4R␣) expression in T helper 2 (TH2) immune responses has not been defined. To examine this role, we infected CD4؉ T-cell IL-4R␣ knockout (KO) mice with the parasitic nematode Nippostrongylus brasiliensis, which induces strong host TH2 responses. Although N. brasiliensis expulsion was not affected in CD4؉ T-cell IL-4R␣ KO mice, the associated lung pathology was reduced. Infected CD4 ؉ T-cell IL-4R␣ KO mice showed abrogation of airway mucus production. T helper type 2 (TH2) immune effector responses are characterized by interleukin-4 (IL-4)-and IL-13-dependent signaling through heterodimeric receptors containing an IL-4 receptor alpha (IL-4R␣) subunit (3). These effector responses are particularly associated with the resolution of helminth infections (16,32,34) and the induction of allergic reactions (12). IL-4R␣ signaling results in activation and upregulation of the transcription factors STAT-6 and GATA-3, which stabilize the TH2 program in polarized CD4 ϩ T cells (3, 27). CD4 ϩ T-cell IL-4R␣-dependent TH2 differentiation is considered to be specific to IL-4, as T cells lack functional IL-13 receptors (43). The resulting TH2 response is characterized by B-cell immunoglobulin E (IgE) and IgG1 antibody production (4, 37), goblet cell hyperplasia (17), and secretion of the TH2 cytokines IL-4, IL-13, IL-5, IL-10, and IL-9 by a number of hematopoietic cells (26). CD4 ϩ T-cell populations and IL-4R␣ expression are essential for the optimal development of TH2 responses (16). However, no requirement for IL-4R␣ expression in T-cell subpopulations for the development of a TH2 response has been demonstrated. Indeed, the interesting observation that there is CD4 ϩ T-cell IL-4R␣-independent IL-4 and IL-13 production has been widely reported (8,15,23,29,31,40). Thus, IL-4-responsive CD4ϩ T cells may not be essential for TH2 polarization (20). In order to examine this possibility, we generated CD4 ϩ T-cell IL-4R␣ transgenic mice with 95.5% Ϯ 5.8% disruption of IL-4R␣ expression on CD4 ϩ T cells (CD4 ϩ T-cell IL-4R␣ knockout [KO] mice) (30). Infection of these mice with Leishmania major indicated that non-IL-4-responsive CD4 ϩ T cells can launch aspects of a TH2 response (30). Additionally, in ovalbumin-induced anaphylaxis (a TH2-associated pathology) T-cell TH2 cytokine secretion appears to be unaffected by IL-4R␣ CD4 ϩ T-cell expression (28). Together, these findings demonstrate that IL-4R␣ expression on CD4 ϩ T cells is not essential for generation of a TH2 immune response.In the study described here we further defined the roles of IL-4-responsive CD4 ϩ T cells by infecting CD4 ϩ T-cell IL-4R␣ KO mice with the nematode Nippostrongylus brasiliensis. N. brasiliensis infections are characterized by a striking IL-4R␣-driven TH2 polarized host immune response which is essential for expulsion of adult worms from the host intestine (35). Importantly, N. brasiliensis infections are analogous to human hookworm infections (e.g., Necator americanus and Ancylostoma duodena...

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CD4+ T Cell-Specific Deletion of IL-4 Receptor α Prevents Ovalbumin-Induced Anaphylaxis by an IFN-γ-Dependent Mechanism

Cited by 23 publications

References 49 publications

Fc Gamma Receptor Signaling in Mast Cells Links Microbial Stimulation to Mucosal Immune Inflammation in the Intestine

Fc Gamma Receptor Signaling in Mast Cells Links Microbial Stimulation to Mucosal Immune Inflammation in the Intestine

Toll-like receptor 2 ligands promote chronic atopic dermatitis through IL-4–mediated suppression of IL-10

Interleukin-4-Promoted T Helper 2 Responses EnhanceNippostrongylus brasiliensis-Induced Pulmonary Pathology

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