Effector memory CD4+T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance

Autor: Yoichiro Iwakura, Yuko Nakamichi, Shigeru Kakuta, Tomohiro Takano, Satoru Uno, Masanori Koide, Shuji Matsuoka, Morita Yoshikazu, Haruyo Nakajima-Adachi, Nobuyuki Udagawa, Kohei Soga, Satoshi Hachimura, Aiko Ono-Ohmachi, Shotaro Nakamura, Hiroshi Kiyono, Takumi Itoh, Masato Tamai, Michio Tomura, Chikao Morimoto, Satoki Yamada
Rok vydání: 2021
Předmět:
Zdroj: Mucosal Immunology. 14:1335-1346
ISSN: 1933-0219
DOI: 10.1038/s41385-021-00434-2
Popis: 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 CD44hiCD62LloCD4+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 CD44hiCD62LloCD4+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 CD44hiCD62LloCD4+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.
Databáze: OpenAIRE
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