title: Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells.
abstract: Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. We report here that, driven by commensal fungi, a wave of CD45(+)CD103(+)RALDH(+) cells migrates to the peripheral lymph nodes after birth. The arrival of these cells introduces high amounts of retinoic acid, mediates the neonatal to adult addressin switch on endothelial cells, and directs the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. In adult mice, a small number of these RALDH(+) cells might serve to maintain the volume of secondary lymphoid organs. Homing deficiency of these cells was associated with lymph node attrition in vitamin-A-deficient mice, suggesting a perpetual dependence on retinoic acid signaling for structural and functional maintenance of peripheral immune organs.
authors.affiliation: Institute for Immunology, Department of Basic Medical Sciences, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zongde
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute for Immunology, Department of Basic Medical Sciences, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Jianjian
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute for Immunology, Department of Basic Medical Sciences, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wencheng
authors.initials: W
authors.lastname: Zheng
authors.affiliation: Institute for Immunology, Department of Basic Medical Sciences, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Institute for Immunology, Department of Basic Medical Sciences, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Institute for Immunology, Department of Basic Medical Sciences, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100730, China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing 100730, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: Institute for Immunology, Department of Basic Medical Sciences, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China; Department of Microbiology, Immunology and Infectious Diseases and Snyder Institute for Chronic Diseases, University of Calgary Calgary, AB T2N 1N4, Canada. Electronic address: yanshi@biomed.tsinghua.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D018821:CD18 Antigens / Q000378:metabolism; D048708:Cell Growth Processes; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000276:immunology; D039001:Integrin alpha Chains / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism; D014801:Vitamin A / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018821:CD18 Antigens; D039001:Integrin alpha Chains; D007527:Isoenzymes; C091367:alpha E integrins; D014801:Vitamin A; D014212:Tretinoin; D000080924:Aldehyde Dehydrogenase 1 Family; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase; D017493:Leukocyte Common Antigens