The development of inducible bronchus-associated lymphoid tissue depends on IL-17

Abstract

Ectopic or tertiary lymphoid tissues, such as inducible bronchus-associated lymphoid tissue (iBALT), form in nonlymphoid organs after local infection or inflammation. However, the initial events that promote this process remain unknown. Here we show that iBALT formed in mouse lungs as a consequence of pulmonary inflammation during the neonatal period. Although we found CD4+CD3 lymphoid tissue–inducer cells (LTi cells) in neonatal lungs, particularly after inflammation, iBALT was formed in mice that lacked LTi cells. Instead, we found that interleukin 17 (IL-17) produced by CD4+ T cells was essential for the formation of iBALT. IL-17 acted by promoting lymphotoxin-α-independent expression of the chemokine CXCL13, which was important for follicle formation. Our results suggest that IL-17-producing T cells are critical for the development of ectopic lymphoid tissues.

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Figure 1: Development of iBALT in neonatal mice rather than adult mice.
Figure 2: Formation of iBALT independently of CCR2 and CCR6.
Figure 3: LTi cells are not required for iBALT development.
Figure 4: Higher expression of IL-17 in neonatal lungs than in adult lungs.
Figure 5: The development of iBALT requires IL-17.
Figure 6: IL-17 acts early in iBALT formation but does not maintain iBALT structure.
Figure 7: IL-17-producing T cells promote iBALT formation.

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Acknowledgements

We thank L. LaMere and A. Boucher for animal husbandry; S. Lira (Mount Sinai School of Medicine) for Ccr6−/− mice; D. Littman (New York University) for Rorc−/− and Id2−/− mice; J. Cyster (University of California, San Francisco) for Cxcl13−/− and plt/plt mice; L. Haynes (Trudeau Institute) for rederived OT-II mice; and J. Browning (Biogen Idec) for soluble LTβR. Supported by the University of Rochester, the US National Institutes of Health (HL069409, AI072689 and AI061511 to T.D.R.; and HL105427 to S.A.K.) and the Children's Hospital of Pittsburgh.

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J.R.-M., D.M.C., M.d.l.L.G.-H. and T.D.R. designed the experiments; J.R.-M., D.M.C., M.d.l.L.G.-H., J.Y.H., K.K. and L.H. did the experiments; J.R.-M. and T.D.R. wrote the paper; and J.K.K., S.A.K. and T.D.R. edited the paper and provided the funding.

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Correspondence to Troy D Randall.

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Rangel-Moreno, J., Carragher, D., de la Luz Garcia-Hernandez, M. et al. The development of inducible bronchus-associated lymphoid tissue depends on IL-17. Nat Immunol 12, 639–646 (2011). https://doi.org/10.1038/ni.2053

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