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Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function

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  • Hung-Wei Cheng

    (Kantonsspital St. Gallen)

  • Urs Mörbe

    (Kantonsspital St. Gallen)

  • Mechthild Lütge

    (Kantonsspital St. Gallen)

  • Céline Engetschwiler

    (Kantonsspital St. Gallen)

  • Lucas Onder

    (Kantonsspital St. Gallen)

  • Mario Novkovic

    (Kantonsspital St. Gallen)

  • Cristina Gil-Cruz

    (Kantonsspital St. Gallen)

  • Christian Perez-Shibayama

    (Kantonsspital St. Gallen)

  • Thomas Hehlgans

    (University of Regensburg)

  • Elke Scandella

    (Kantonsspital St. Gallen)

  • Burkhard Ludewig

    (Kantonsspital St. Gallen)

Abstract

Innate lymphoid cells (ILCs) govern immune cell homeostasis in the intestine and protect the host against microbial pathogens. Various cell-intrinsic pathways have been identified that determine ILC development and differentiation. However, the cellular components that regulate ILC sustenance and function in the intestinal lamina propria are less known. Using single-cell transcriptomic analysis of lamina propria fibroblasts, we identify fibroblastic reticular cells (FRCs) that underpin cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Genetic ablation of lymphotoxin-β receptor expression in Ccl19-expressing FRCs blocks the maturation of CPs into mature ILFs. Interactome analysis shows the major niche factors and processes underlying FRC-ILC crosstalk. In vivo validation confirms that a sustained lymphotoxin-driven feedforward loop of FRC activation including IL-7 generation is critical for the maintenance of functional ILC populations. In sum, our study indicates critical fibroblastic niches within the intestinal lamina propria that control ILC homeostasis and functionality and thereby secure protective gut immunity.

Suggested Citation

  • Hung-Wei Cheng & Urs Mörbe & Mechthild Lütge & Céline Engetschwiler & Lucas Onder & Mario Novkovic & Cristina Gil-Cruz & Christian Perez-Shibayama & Thomas Hehlgans & Elke Scandella & Burkhard Ludewig, 2022. "Intestinal fibroblastic reticular cell niches control innate lymphoid cell homeostasis and function," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29734-2
    DOI: 10.1038/s41467-022-29734-2
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