1. Effector memory CD4 + T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance.
- Author
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Ono-Ohmachi A, Yamada S, Uno S, Tamai M, Soga K, Nakamura S, Udagawa N, Nakamichi Y, Koide M, Morita Y, Takano T, Itoh T, Kakuta S, Morimoto C, Matsuoka S, Iwakura Y, Tomura M, Kiyono H, Hachimura S, and Nakajima-Adachi H
- Subjects
- Animals, Biomarkers, Bone Resorption diagnostic imaging, Bone Resorption metabolism, Bone Resorption pathology, Cytokines genetics, Cytokines metabolism, Disease Models, Animal, Disease Susceptibility, Food Hypersensitivity metabolism, Immunophenotyping, Interleukin-4 metabolism, Intestinal Diseases complications, Intestinal Diseases metabolism, Lymph Nodes metabolism, Mesentery, Mice, Models, Biological, Bone Resorption etiology, CD4-Positive T-Lymphocytes physiology, Food Hypersensitivity complications, Food Hypersensitivity immunology, Interleukin-4 genetics, Intestinal Diseases immunology, Lymph Nodes immunology, Memory T Cells physiology
- Abstract
Intestinal inflammation can be accompanied by osteoporosis, but their relationship, mediated by immune responses, remains unclear. Here, we investigated a non-IgE-mediated food-allergic enteropathy model of ovalbumin (OVA) 23-3 mice expressing OVA-specific T-cell-receptor transgenes. Mesenteric lymph nodes (MLNs) and their pathogenic CD4
+ T cells were important to enteropathy occurrence and exacerbation when the mice were fed an egg-white (EW) diet. EW-fed OVA23-3 mice also developed bone loss and increased CD44hi CD62Llo CD4+ T cells in the MLNs and bone marrow (BM); these changes were attenuated by MLN, but not spleen, resection. We fed an EW diet to F1 cross offspring from OVA23-3 mice and a mouse line expressing the photoconvertible protein KikGR to track MLN CD4+ T cells. Photoconverted MLN CD44hi CD62Llo CD4+ T cells migrated predominantly to the BM; pit formation assay proved their ability to promote bone damage via osteoclasts. Significantly greater expression of IL-4 mRNA in MLN CD44hi CD62Llo CD4+ T cells and bone was observed in EW-fed OVA23-3 mice. Anti-IL-4 monoclonal antibody injection canceled bone loss in the primary inflammation phase in EW-fed mice, but less so in the chronic phase. This novel report shows the specific inflammatory relationship, via Th2-dominant-OVA-specific T cells and IL-4 production, between MLNs and bone, a distant organ, in food-allergic enteropathy., (© 2021. The Author(s), under exclusive licence to Society for Mucosal Immunology.)- Published
- 2021
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