First Author | Eddens T | Year | 2017 |
Journal | Cell Rep | Volume | 18 |
Issue | 13 | Pages | 3078-3090 |
PubMed ID | 28355561 | Mgi Jnum | J:254037 |
Mgi Id | MGI:6103238 | Doi | 10.1016/j.celrep.2017.03.016 |
Citation | Eddens T, et al. (2017) Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity. Cell Rep 18(13):3078-3090 |
abstractText | 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. |