日本庆应义塾大学Koji Hase团队发现禁食与再喂食能够影响免疫细胞动态和粘膜免疫反应。这一研究成果于2019年8月22日发表在国际学术期刊《细胞》上。
研究人员发现,暂时的禁食减少了派伊尔结(即肠道免疫反应的诱导部位)处约50%淋巴细胞。随后的再次喂食似乎恢复了淋巴细胞的数量,但其细胞组成明显改变。在禁食期间,大部分生发中心的和IgA阳性的B细胞通过细胞凋亡而减少。同时,初始B细胞在禁食期间从PP迁移至骨髓;然后在再喂食期间,当间质细胞检测到营养信号并上调CXCL13表达以募集初始B细胞时,又重新返回PP。此外,在卵白蛋白口服免疫前,短暂的禁食抑制了抗原特异性IgA的诱导,并无法引起口服耐受,最终加剧食物抗原诱导的腹泻。因此,营养信号对于维持肠道免疫稳态至关重要。
研究人员表示,营养状况可能会影响免疫反应; 然而,营养信号如何调节细胞动态和功能仍然不清楚。
附:英文原文
Title: Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses
Author: Motoyoshi Nagai,Ryotaro Noguchi,Daisuke Takahashi,Takayuki Morikawa,Kouhei Koshida,Seiga Komiyama,Narumi Ishihara,Takahiro Yamada,Yuki I. Kawamura,Kisara Muroi,Kouya Hattori,Nobuhide Kobayashi,Yumiko Fujimura,Masato Hirota,Ryohtaroh Matsumoto,Ryo Aoki,Miwa Tamura-Nakano,Machiko Sugiyama,Tomoya Katakai,Shintaro Sato,Keiyo Takubo,Taeko Dohi,Koji Hase
Issue&Volume:Volume 178 Issue 5
Abstract: Nutritional status potentially influences immune responses; however, how nutritional signals regulate cellular dynamics and functionality remains obscure. Herein, we report that temporary fasting drastically reduces the number of lymphocytes by ~50% in Peyer’s patches (PPs), the inductive site of the gut immune response. Subsequent refeeding seemingly restored the number of lymphocytes, but whose cellular composition was conspicuously altered. A large portion of germinal center and IgA+ B cells were lost via apoptosis during fasting. Meanwhile, naive B cells migrated from PPs to the bone marrow during fasting and then back to PPs during refeeding when stromal cells sensed nutritional signals and upregulated CXCL13 expression to recruit naive B cells. Furthermore, temporal fasting before oral immunization with ovalbumin abolished the induction of antigen-specific IgA, failed to induce oral tolerance, and eventually exacerbated food antigen-induced diarrhea. Thus, nutritional signals are critical in maintaining gut immune homeostasis.
DOI: https://doi.org/10.1016/j.cell.2019.07.047
Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30847-5#