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

Guang-Hui Liu ,. et al. 2011. Nature 472, 221–225

Speaker: Zhou Yu(周 妤)                                              Time: 13:00~14:00, Octet 27, 2011

Commentator: Dr. Jiu-Yao Wang (王志堯醫師)          Place: Room 601

Abstract:

Inducible bronchus-associated lymphoid tissue (iBALT) formed in the lungs after pulmonary inflammation of infection of mice and humans is often association with chronic disease, such as rheumatoid arthritis, tuberculosis and chronic obstructive pulmonary disease. According to published papers, the maintenance of iBALT is dependent on CD11c⁺ DCs but little is known about the cell types involved in the initial step of the ectopic lymphoid tissues formation. In this study, the authors administered LPS intranasally to mice as neonates and then again as 6-week-old adults to generate well-defined iBALT in pulmonary. In the begining, they found that iBALT developed normally in Ccr2-/- and Ccr6-/- mice, although both chemokine receptors play roles in recruitment of monocytes and DCs. Then, they also found iBALT was formed in transgenic mice which are lacking of CD4+CD3- lymphoid tissue-inducer cells (LiT cells), a well-known cell type for promoting the development of conventional lymphoid nodes. Meanwhile, the authors found higher IL-23p19 and IL-17A expressions in neonates than in adults, which suggested that IL-17-producing T cells may promote the formation of iBALT. So they used IL-17 receptor A- and IL-17A-deficient mice to show reduced number and size of lymphoid areas, B cell follicles and FDC networks after LPS administration to demonstrate IL-17 contributes to iBALT formation. They also showed isolated pulmonary fibroblasts from wild-type neonatal mice could express high levels of CXCL13 and CCL19 but not of CCL21 after treating with recombinant IL-17A. They further proved IL-17 signaling is involved in the initiation of iBALT formation by using IL-17A blocking antibody given beforeiBALT formation in wild-type mice. By probing sections of LPS-treated neonatal lungs with anti-IL-17A, they found all IL-17-producing cells in developing iBALT area expressed CD4. Finally, they found the iBALT formation was few and small in T cell-deficient (Tcrb-/-Tcrd-/-) mice and the phenomenon was reversed when the deficient mice were adoptively transferred with CD4+ T cells from LPS-treated mice. In conclusion, they established a model of ectopic lymphoid tissues which develoment is critcally required IL-17-producing T cells that could provide a possible therapeutic target for chronic disease.

References:

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2.      Van de Pavert, S.A., et al. 2009. Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat. Immunol. 10, 1193–1199.