Kiyoshi Yamazaki, MD, Joseph A. Murray, MD, Hirohito Kita, MD

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Presentation transcript:

Innate immunomodulatory effects of cereal grains through induction of IL-10 Kiyoshi Yamazaki, MD, Joseph A. Murray, MD, Hirohito Kita, MD Journal of Allergy and Clinical Immunology Volume 121, Issue 1, Pages 172-178.e3 (January 2008) DOI: 10.1016/j.jaci.2007.08.031 Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Allergen extract– and Con A–induced cytokine production from PBMCs. PBMCs were incubated with allergen extracts or Con A. The box plots summarize 20 healthy individuals, the line represents the median (50th percentile), and the lower whisker, lower hinge, upper hinge, and upper whisker represent the 10th, 25th, 75th, and 90th percentiles, respectively. Asp, Aspergillus fumigatus. Journal of Allergy and Clinical Immunology 2008 121, 172-178.e3DOI: (10.1016/j.jaci.2007.08.031) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Effects of glycerinated cereal grain extracts (A) and lyophilized cereal grain and nongrain extracts (B) on IL-10 production from PBMCs. In Fig 2, A, PBMCs were incubated with glycerinated or reconstituted lyophilized (Ly) wheat or rice extracts. Glycerinated extracts were from 4 sources (A-D). In Fig 2, B, PBMCs were incubated with 6 grains (wheat, rice, rye, buckwheat, oat, and corn), HDM, and milk extracts. Values are presented as means and SEs (n = 3 different individuals). Journal of Allergy and Clinical Immunology 2008 121, 172-178.e3DOI: (10.1016/j.jaci.2007.08.031) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Monocytes in PBMCs stimulated with grain extracts produce IL-10 and might inhibit IFN-γ. A, PBMCs were stimulated with rice extract or Con A and stained intracellularly with PE-conjugated anti-IL-10 and extracellularly with FITC-conjugated anti-CD14. Representative dot plots show 1 donor from 3 different individuals. B, PBMCs and monocyte-depleted PBMCs were incubated with rice or wheat extract. Values are presented as means and SEs (n = 3 different individuals). Ab, Antibody. Journal of Allergy and Clinical Immunology 2008 121, 172-178.e3DOI: (10.1016/j.jaci.2007.08.031) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Wheat extract inhibits Con A–induced production of IL-5, IL-13, and IFN-γ and enhances IL-10 production from PBMCs. PBMCs were incubated with Con A and various concentrations of wheat extract. Each line represents one of 4 different healthy donors; results are normalized to no wheat as 100%. Journal of Allergy and Clinical Immunology 2008 121, 172-178.e3DOI: (10.1016/j.jaci.2007.08.031) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Anti-IL-10 reverses the wheat-induced inhibition of Con A–stimulated cytokine production. PBMCs from healthy donors were incubated with Con A with or without wheat extract and anti-human IL-10 or control IgG. Data are normalized to the levels induced by Con A as 100%. Results show 1 representative experiment of 3 experiments. Ab, Antibody. Journal of Allergy and Clinical Immunology 2008 121, 172-178.e3DOI: (10.1016/j.jaci.2007.08.031) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 6 Effects of monocyte reconstitution on Con A–induced production of cytokines by CD4+ T cells. Isolated CD4+ T cells were incubated with Con A or Con A plus wheat extract. Different numbers of CD14+ monocytes were reconstituted into the CD4+ T cells. Results show 1 representative experiment of 3 experiments. Journal of Allergy and Clinical Immunology 2008 121, 172-178.e3DOI: (10.1016/j.jaci.2007.08.031) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 7 Anti-TLR4 inhibits cereal grain–induced IL-10 production from PBMCs. PBMCs were incubated with rice, wheat, or LPS with or without anti-TLR4 antibody or control IgG. Results are normalized to no antibody as 100%. Values are presented as means and SEs (n = 3 different individuals). ∗P < .05 compared with control IgG. Ab, Antibody. Journal of Allergy and Clinical Immunology 2008 121, 172-178.e3DOI: (10.1016/j.jaci.2007.08.031) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

IL-10 production from PBMCs in response to commercial foods IL-10 production from PBMCs in response to commercial foods. Food extracts (cereal grains, flours, bread, cereals, and soy products) were incubated with PBMCs (2 × 106 cells/mL) for 24 hours. Results show means with SEs of 3 experiments using PBMCs from 3 different individuals. Mortar wash solution (PBS), treated similarly, was used as a control. Journal of Allergy and Clinical Immunology 2008 121, 172-178.e3DOI: (10.1016/j.jaci.2007.08.031) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Effects of lectins, rice extract, and wheat extract on Con A–induced cytokine production from PBMCs. PBMCs (2 × 106 cells/mL) were incubated with Con A (5 μg/mL) with or without 10 μg/mL PHA, wheat germ agglutinin (WGA), rice extract, or wheat extract for 96 hours at 37°C. Each column represents means ± SEM from 3 experiments using PBMCs from healthy donors; results are normalized to Con A alone (no inhibitors) as 100%. ∗P < .05 and ∗∗P < .01 compared with Con A alone. Journal of Allergy and Clinical Immunology 2008 121, 172-178.e3DOI: (10.1016/j.jaci.2007.08.031) Copyright © 2008 American Academy of Allergy, Asthma & Immunology Terms and Conditions