title: IL-17-induced CXCL12 recruits B cells and induces follicle formation in BALT in the absence of differentiated FDCs.
abstract: Ectopic lymphoid tissue, such as bronchus-associated lymphoid tissue (BALT) in the lung, develops spontaneously at sites of chronic inflammation or during infection. The molecular mechanisms underlying the neogenesis of such tertiary lymphoid tissue are still poorly understood. We show that the type of inflammation-inducing pathogen determines which key factors are required for the formation and maturation of BALT. Thus, a single intranasal administration of the poxvirus modified vaccinia virus Ankara (MVA) is sufficient to induce highly organized BALT with densely packed B cell follicles containing a network of CXCL13-expressing follicular DCs (FDCs), as well as CXCL12-producing follicular stromal cells. In contrast, mice treated with P. aeruginosa (P.a.) develop BALT but B cell follicles lack FDCs while still harboring CXCL12-positive follicular stromal cells. Furthermore, in IL-17-deficient mice, P.a.-induced BALT largely lacks B cells as well as CXCL12-expressing stromal cells, and only loose infiltrates of T cells are present. We show that Toll-like receptor pathways are required for BALT induction by P.a., but not MVA, and provide evidence that IL-17 drives the differentiation of lung stroma toward podoplanin-positive CXCL12-expressing cells that allow follicle formation even in the absence of FDCs. Taken together, our results identify distinct pathogen-dependent induction and maturation pathways for BALT formation.
authors.affiliation: Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Henrike
authors.initials: H
authors.lastname: Fleige
authors.forename: Sarina
authors.initials: S
authors.lastname: Ravens
authors.forename: Georgios Leandros
authors.initials: GL
authors.lastname: Moschovakis
authors.forename: Jasmin
authors.initials: J
authors.lastname: Bölter
authors.forename: Stefanie
authors.initials: S
authors.lastname: Willenzon
authors.forename: Gerd
authors.initials: G
authors.lastname: Sutter
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kalinke
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001980:Bronchi / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002642:Chick Embryo; D020566:Dendritic Cells, Follicular / Q000166:cytology* / Q000276:immunology; D020381:Interleukin-17 / Q000378:metabolism*; D008221:Lymphoid Tissue / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000502:physiology; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D054377:Chemokine CXCL12; D020381:Interleukin-17; D053594:Myeloid Differentiation Factor 88; D019718:Receptors, CXCR4; C476286:Ticam1 protein, mouse