[PDF][PDF] Pneumocystis-driven inducible bronchus-associated lymphoid tissue formation requires Th2 and Th17 immunity

T Eddens, W Elsegeiny, M de la Luz Garcia-Hernadez… - Cell reports, 2017 - cell.com
T Eddens, W Elsegeiny, M de la Luz Garcia-Hernadez, P Castillo, G Trevejo-Nunez…
Cell reports, 2017cell.com
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 …
Summary
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.
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