1. T helper cell IL-4 drives intestinal Th2 priming to oral peanut antigen, under the control of OX40L and independent of innate-like lymphocytes.
- Author
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Chu DK, Mohammed-Ali Z, Jiménez-Saiz R, Walker TD, Goncharova S, Llop-Guevara A, Kong J, Gordon ME, Barra NG, Gillgrass AE, Van Seggelen H, Khan WI, Ashkar AA, Bramson JL, Humbles AA, Kolbeck R, Waserman S, and Jordana M
- Subjects
- Allergens chemistry, Animals, Eosinophils immunology, Eosinophils pathology, Immunity, Innate, Immunoglobulin E immunology, Immunoglobulin G immunology, Interleukin-13 genetics, Interleukin-13 immunology, Interleukin-4 genetics, Intestines pathology, Membrane Glycoproteins genetics, Mice, Mice, Knockout, OX40 Ligand, Peanut Hypersensitivity pathology, Receptors, Antigen, T-Cell, gamma-delta genetics, Receptors, Antigen, T-Cell, gamma-delta immunology, Th2 Cells pathology, Tumor Necrosis Factors genetics, Allergens immunology, Arachis chemistry, Interleukin-4 immunology, Intestines immunology, Membrane Glycoproteins immunology, Peanut Hypersensitivity immunology, Th2 Cells immunology, Tumor Necrosis Factors immunology
- Abstract
Intestinal T helper type 2 (Th2) immunity in food allergy results in IgG1 and IgE production, and antigen re-exposure elicits responses such as anaphylaxis and eosinophilic inflammation. Although interleukin-4 (IL-4) is critically required for allergic sensitization, the source and control of IL-4 during the initiation of Th2 immunity in vivo remains unclear. Non-intestinal and non-food allergy systems have suggested that natural killer-like T (NKT) or γδ T-cell innate lymphocytes can supply the IL-4 required to induce Th2 polarization. Group 2 innate lymphoid cells (ILCs) are a novel IL-4-competent population, but their contribution to initiating adaptive Th2 immunity is unclear. There are also reports of IL-4-independent Th2 responses. Here, we show that IL-4-dependent peanut allergic Th2 responses are completely intact in NKT-deficient, γδ T-deficient or ILC-deficient mice, including antigen-specific IgG1/IgE production, anaphylaxis, and cytokine production. Instead, IL-4 solely from CD4(+) Th cells induces full Th2 immunity. Further, CD4(+) Th cell production of IL-4 in vivo is dependent on OX40L, a costimulatory molecule on dendritic cells (DCs) required for intestinal allergic priming. However, both Th2 cells and ILCs orchestrated IL-13-dependent eosinophilic inflammation. Thus, intestinal Th2 priming is initiated by an autocrine/paracrine acting CD4(+) Th cell-intrinsic IL-4 program that is controlled by DC OX40L, and not by NKT, γδ T, or ILC cells.
- Published
- 2014
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