Effector memory CD4+T cells in mesenteric lymph nodes mediate bone loss in food-allergic enteropathy model mice, creating IL-4 dominance
Aiko Ono-Ohmachi, Satoki Yamada, Satoru Uno, Masato Tamai, Kohei Soga, Shotaro Nakamura, Nobuyuki Udagawa, Yuko Nakamichi, Masanori Koide, Yoshikazu Morita, Tomohiro Takano, Takumi Itoh, Shigeru Kakuta, Chikao Morimoto, Shuji Matsuoka, Yoichiro Iwakura, Michio Tomura, Hiroshi Kiyono, Satoshi Hachimura, Haruyo Nakajima-Adachi*
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.
- : Mucosal Immunology
- : 10.1038/s41385-021-00434-2
- : https://www.nature.com/articles/s41385-021-00434-2?proof=t