T helper cell IL-4 drives intestinal Th2 priming to oral peanut antigen, under the control of OX40L and independent of innate-like lymphocytes
doi: 10.1038/mi.2014.29
pmid: 24781052
T helper cell IL-4 drives intestinal Th2 priming to oral peanut antigen, under the control of OX40L and independent of innate-like lymphocytes
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.
- MedImmune United States
- McMaster University Canada
Mice, Knockout, Interleukin-13, Membrane Glycoproteins, Arachis, OX40 Ligand, Receptors, Antigen, T-Cell, gamma-delta, Allergens, Immunoglobulin E, Immunity, Innate, Eosinophils, Intestines, Mice, Th2 Cells, Immunoglobulin G, Tumor Necrosis Factors, Animals, Peanut Hypersensitivity, Interleukin-4
Mice, Knockout, Interleukin-13, Membrane Glycoproteins, Arachis, OX40 Ligand, Receptors, Antigen, T-Cell, gamma-delta, Allergens, Immunoglobulin E, Immunity, Innate, Eosinophils, Intestines, Mice, Th2 Cells, Immunoglobulin G, Tumor Necrosis Factors, Animals, Peanut Hypersensitivity, Interleukin-4
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