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

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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Publication Details

Journal
bioRxiv (Cold Spring Harbor Laboratory)
Published
2026-11-02
DOI
https://doi.org/10.64898/2026.10.28.762535
Primary Topic
T-cell and B-cell Immunology
Type
preprint
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preprint

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

Viral S. Shah, Jackson A. Weir, Anthony Xu, Giovanni J. Marrero et al.
1 links
bioRxiv (Cold Spring Harbor Laboratory)
T-cell and B-cell Immunology
preprint

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

Viral S. Shah, Jackson A. Weir, Anthony Xu, Giovanni J. Marrero, Dawei Sun, Brian Lin, Jason W. Griffith, Qiaozhen Liu, Jayaraj Rajagopal, Steven Zwick, Vipin Kumar, Manalee Vishnu Surve, Victoria I Cottrell, Fei Chen, H. Willit, Tivadar Torok, Vanshika Panchal, John Vo Huynh, Sunghyun Kim, Po Kwok Tse, Jiawei Sun
preprint en

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.

bioRxiv (Cold Spring Harbor Laboratory)
Broad Institute (US), Tufts University (US), Princeton University (US), Massachusetts General Hospital (US), Harvard Stem Cell Institute (US), University of Pennsylvania (US)
Good health and well-being
T-cell and B-cell Immunology
DOIOpen Access PDFOpenAlex
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