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PreprintCC BY-NC-NDbioRxiv

Induced microfold cells are required for the function of pulmonary tertiary lymphoid organs that promote mucosal immunity

  • M. V. Surve
  • D. Sun
  • V. Panchal
  • B. Lin
  • P. K. Tse
  • S. Kim
  • Q. Liu
  • T. Török
  • J. A. Weir
  • A. Xu
  • J. V. Huynh
  • V. I. Cottrell
9 more authors
  • H. Willit
  • G. Marrero
  • V. Kumar
  • J. Sun
  • S. Zwick
  • V. S. Shah
  • J. W. Griffith
  • F. Chen
  • J. Rajagopal1
  1. 1Department of Medicine, Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, USA
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Abstract

Tertiary lymphoid organs (TLOs) arise in response to infection and inflammation. We show that influenza-induced lung TLOs are comprised of inducible M cell (iM cell)-inducible bronchus-associated lymphoid tissue (iBALT) functional composites. iM cells are necessary for the appropriate architecture of adjacent immune follicles, which contain clonally expanded and sequence-diversified B cells. iM cell ablation results in fewer antigen-specific germinal center B cells, T follicular helper cells, and T helper memory cells, and a decrease in secretory IgA and IgG production accompanied by a loss of viral control. We find that the iM cells arise from epithelial progenitors that respond to a RANKL signal from infiltrating T cells, consistent with a model in which the patchy inflammation typical of pneumonia results in the unpredictable and varying distribution of coupled iM cells and adjacent iBALT. We propose that iM cells could be harnessed to promote infection control and enhance mucosal vaccination.

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Cite

BibTeXRIS
BibTeX
@misc{surve2026induced,
  title = {{Induced microfold cells are required for the function of pulmonary tertiary lymphoid organs that promote mucosal immunity}},
  author = {M. V. Surve and D. Sun and V. Panchal and B. Lin and P. K. Tse and S. Kim and Q. Liu and T. Török and J. A. Weir and A. Xu and J. V. Huynh and V. I. Cottrell and H. Willit and G. Marrero and V. Kumar and J. Sun and S. Zwick and V. S. Shah and J. W. Griffith and F. Chen and J. Rajagopal},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.28.762535},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.28.762535v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Induced microfold cells are required for the function of pulmonary tertiary lymphoid organs that promote mucosal immunity
AU  - M. V. Surve
AU  - D. Sun
AU  - V. Panchal
AU  - B. Lin
AU  - P. K. Tse
AU  - S. Kim
AU  - Q. Liu
AU  - T. Török
AU  - J. A. Weir
AU  - A. Xu
AU  - J. V. Huynh
AU  - V. I. Cottrell
AU  - H. Willit
AU  - G. Marrero
AU  - V. Kumar
AU  - J. Sun
AU  - S. Zwick
AU  - V. S. Shah
AU  - J. W. Griffith
AU  - F. Chen
AU  - J. Rajagopal
PY  - 2026
DA  - 2026/10/28
PB  - bioRxiv
DO  - 10.64898/2026.10.28.762535
UR  - https://www.biorxiv.org/content/10.64898/2026.10.28.762535v1
AB  - Tertiary lymphoid organs (TLOs) arise in response to infection and inflammation. We show that influenza-induced lung TLOs are comprised of inducible M cell (iM cell)-inducible bronchus-associated lymphoid tissue (iBALT) functional composites. iM cells are necessary for the appropriate architecture of adjacent immune follicles, which contain clonally expanded and sequence-diversified B cells. iM cell ablation results in fewer antigen-specific germinal center B cells, T follicular helper cells, and T helper memory cells, and a decrease in secretory IgA and IgG production accompanied by a loss of viral control. We find that the iM cells arise from epithelial progenitors that respond to a RANKL signal from infiltrating T cells, consistent with a model in which the patchy inflammation typical of pneumonia results in the unpredictable and varying distribution of coupled iM cells and adjacent iBALT. We propose that iM cells could be harnessed to promote infection control and enhance mucosal vaccination.
ER  -