title: Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity.
abstract: Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic lymphoid structure composed of highly organized T cell and B cell zones that forms in the lung in response to infectious or inflammatory stimuli. Here, we develop a model for fungal-mediated iBALT formation, using infection with Pneumocystis that induces development of pulmonary lymphoid follicles. Pneumocystis-dependent iBALT structure formation and organization required CXCL13 signaling. Cxcl13 expression was regulated by interleukin (IL)-17 family members, as Il17ra-/-, Il17rb-/-, and Il17rc-/-mice failed to develop iBALT. Interestingly, Il17rb-/-mice have intact Th17 responses, but failed to generate an anti-Pneumocystis Th2 response. Given a role for Th2 and Th17 immunity in iBALT formation, we demonstrated that primary pulmonary fibroblasts synergistically upregulated Cxcl13 transcription following dual stimulation with IL-13 and IL-17A in a STAT3/GATA3-dependent manner. Together, these findings uncover a role for Th2/Th17 cells in regulating Cxcl13 expression and provide an experimental model for fungal-driven iBALT formation.
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Eddens
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
authors.forename: Waleed
authors.initials: W
authors.lastname: Elsegeiny
authors.affiliation: Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester, Rochester, NY 14624, USA.
authors.forename: Maria de la Luz
authors.initials: ML
authors.lastname: Garcia-Hernadez
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Castillo
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
authors.forename: Giraldina
authors.initials: G
authors.lastname: Trevejo-Nunez
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
authors.forename: Katelin
authors.initials: K
authors.lastname: Serody
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Campfield
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Shabaana A
authors.initials: SA
authors.lastname: Khader
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA.
authors.forename: Kong
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Medicine, Allergy/Immunology, and Rheumatology, University of Rochester, Rochester, NY 14624, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Rangel-Moreno
authors.affiliation: Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15224, USA. Electronic address: jay.kolls@chp.edu.
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
mesh_terms: D000818:Animals; D001980:Bronchi / Q000473:pathology*; D054382:Chemokine CXCL13 / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000378:metabolism; D007109:Immunity; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008221:Lymphoid Tissue / Q000473:pathology*; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011010:Pneumocystis / Q000502:physiology*; D016720:Pneumocystis Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D054380:Receptors, CXCR5 / Q000378:metabolism; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: C513179:CXCR5 protein, mouse; D054382:Chemokine CXCL13; D050990:GATA3 Transcription Factor; D018793:Interleukin-13; D020381:Interleukin-17; D008233:Lymphotoxin-alpha; D054380:Receptors, CXCR5; D053722:Receptors, Interleukin-17; D050796:STAT3 Transcription Factor
keywords: Cxcl13; Pneumocystis; Th17; Th2; fungus; iBALT; immunity; lymphoid tissue