TY - JOUR TI - Effector memory CD4+T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance AU - Ono-Ohmachi, Aiko AU - Yamada, Satoki AU - Uno, Satoru AU - Tamai, Masato AU - Soga, Kohei AU - Nakamura, Shotaro AU - Udagawa, Nobuyuki AU - Nakamichi, Yuko AU - Koide, Masanori AU - Morita, Yoshikazu AU - Takano, Tomohiro AU - Itoh, Takumi AU - Kakuta, Shigeru AU - Morimoto, Chikao AU - Matsuoka, Shuji AU - Iwakura, Yoichiro AU - Tomura, Michio AU - Kiyono, Hiroshi AU - Hachimura, Satoshi AU - Nakajima-Adachi, Haruyo T2 - Mucosal Immunology AB - 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. DA - 2021/07/29/ PY - 2021 DO - 10.1038/s41385-021-00434-2 DP - www.nature.com SP - 1 EP - 12 J2 - Mucosal Immunol LA - en SN - 1935-3456 UR - https://www.nature.com/articles/s41385-021-00434-2 Y2 - 2021/07/29/16:50:29 ER -