Sustained innate interferon is an essential inducer of tertiary lymphoid structures.

Autor: Calvanese AL; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Cecconi V; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Stäheli S; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Schnepf D; Institute of Virology, Medical Center University of Freiburg, Freiburg im Breisgau, Germany., Nater M; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Pereira P; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland., Gschwend J; Institute of Physiology, University of Zurich, Zurich, Switzerland., Heikenwälder M; Division of Chronic Inflammation and Cancer, German Cancer Research Center Heidelberg (DKFZ), Heidelberg, Germany.; M3 Research Institute, Eberhard Karls University Tübingen, Tübingen, Germany., Schneider C; Institute of Physiology, University of Zurich, Zurich, Switzerland., Ludewig B; Institute of Immunobiology, Medical Research Center, Kantonsspital St. Gallen, St. Gallen, Switzerland., Silina K; Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, Switzerland., van den Broek M; Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2024 Oct; Vol. 54 (10), pp. e2451207. Date of Electronic Publication: 2024 Jul 09.
DOI: 10.1002/eji.202451207
Abstrakt: Tertiary lymphoid structures (TLS) resemble follicles of secondary lymphoid organs and develop in nonlymphoid tissues during inflammation and cancer. Which cell types and signals drive the development of TLS is largely unknown. To investigate early events of TLS development in the lungs, we repeatedly instilled p(I:C) plus ovalbumin (Ova) intranasally. This induced TLS ranging from lymphocytic aggregates to organized and functional structures containing germinal centers. We found that TLS development is independent of FAP + fibroblasts, alveolar macrophages, or CCL19 but crucially depends on type I interferon (IFN-I). Mechanistically, IFN-I initiates two synergistic pathways that culminate in the development of TLS. On the one hand, IFN-I induces lymphotoxin (LT)α in lymphoid cells, which stimulate stromal cells to produce the B-cell-attracting chemokine CXCL13 through LTβR-signaling. On the other hand, IFN-I is sensed by stromal cells that produce the T-cell-attracting chemokines CXCL9, CXCL10 as well as CCL19 and CCL21 independently of LTβR. Consequently, B-cell aggregates develop within a week, whereas follicular dendritic cells and germinal centers appear after 3 weeks. Thus, sustained production of IFN-I together with an antigen is essential for the induction of functional TLS in the lungs.
(© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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