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Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis

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Listed:
  • Pai Wang

    (Changchun
    Yale University)

  • Xin Yang

    (Yale University
    Shanghai Jiao Tong University)

  • Luyao Zhang

    (Changchun
    Yale University)

  • Sha Sha

    (Yale University
    The First Affiliated Hospital of Shandong First Medical University)

  • Juan Huang

    (Yale University)

  • Jian Peng

    (Yale University)

  • Jianlei Gu

    (Yale School of Public Health)

  • James Alexander Pearson

    (Yale University
    Cardiff University)

  • Youjia Hu

    (Yale University)

  • Hongyu Zhao

    (Yale School of Public Health)

  • F. Susan Wong

    (Cardiff University)

  • Quan Wang

    (Changchun)

  • Li Wen

    (Yale University)

Abstract

Toll-like receptor 9 (TLR9) recognizes bacterial, viral and self DNA and play an important role in immunity and inflammation. However, the role of TLR9 in obesity is less well-studied. Here, we generate B-cell-specific Tlr9-deficient (Tlr9fl/fl/Cd19Cre+/-, KO) B6 mice and model obesity using a high-fat diet. Compared with control mice, B-cell-specific-Tlr9-deficient mice exhibited increased fat tissue inflammation, weight gain, and impaired glucose and insulin tolerance. Furthermore, the frequencies of IL-10-producing-B cells and marginal zone B cells were reduced, and those of follicular and germinal center B cells were increased. This was associated with increased frequencies of IFNγ-producing-T cells and increased follicular helper cells. In addition, gut microbiota from the KO mice induced a pro-inflammatory state leading to immunological and metabolic dysregulation when transferred to germ-free mice. Using 16 S rRNA gene sequencing, we identify altered gut microbial communities including reduced Lachnospiraceae, which may play a role in altered metabolism in KO mice. We identify an important network involving Tlr9, Irf4 and Il-10 interconnecting metabolic homeostasis, with the function of B and T cells, and gut microbiota in obesity.

Suggested Citation

  • Pai Wang & Xin Yang & Luyao Zhang & Sha Sha & Juan Huang & Jian Peng & Jianlei Gu & James Alexander Pearson & Youjia Hu & Hongyu Zhao & F. Susan Wong & Quan Wang & Li Wen, 2024. "Tlr9 deficiency in B cells leads to obesity by promoting inflammation and gut dysbiosis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48611-8
    DOI: 10.1038/s41467-024-48611-8
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    1. Helen Luck & Saad Khan & Justin H. Kim & Julia K. Copeland & Xavier S. Revelo & Sue Tsai & Mainak Chakraborty & Kathleen Cheng & Yi Tao Chan & Mark K. Nøhr & Xavier Clemente-Casares & Marie-Christine , 2019. "Gut-associated IgA+ immune cells regulate obesity-related insulin resistance," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    2. Deepak A. Rao & Michael F. Gurish & Jennifer L. Marshall & Kamil Slowikowski & Chamith Y. Fonseka & Yanyan Liu & Laura T. Donlin & Lauren A. Henderson & Kevin Wei & Fumitaka Mizoguchi & Nikola C. Tesl, 2017. "Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis," Nature, Nature, vol. 542(7639), pages 110-114, February.
    3. Peter J. Turnbaugh & Ruth E. Ley & Michael A. Mahowald & Vincent Magrini & Elaine R. Mardis & Jeffrey I. Gordon, 2006. "An obesity-associated gut microbiome with increased capacity for energy harvest," Nature, Nature, vol. 444(7122), pages 1027-1031, December.
    4. Jonas Schluter & Jonathan U. Peled & Bradford P. Taylor & Kate A. Markey & Melody Smith & Ying Taur & Rene Niehus & Anna Staffas & Anqi Dai & Emily Fontana & Luigi A. Amoretti & Roberta J. Wright & Se, 2020. "The gut microbiota is associated with immune cell dynamics in humans," Nature, Nature, vol. 588(7837), pages 303-307, December.
    5. Hiroaki Hemmi & Osamu Takeuchi & Taro Kawai & Tsuneyasu Kaisho & Shintaro Sato & Hideki Sanjo & Makoto Matsumoto & Katsuaki Hoshino & Hermann Wagner & Kiyoshi Takeda & Shizuo Akira, 2000. "A Toll-like receptor recognizes bacterial DNA," Nature, Nature, vol. 408(6813), pages 740-745, December.
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