Journal
CELL REPORTS
Volume 18, Issue 13, Pages 3078-3090Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.03.016
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Funding
- NIH [F30AI114146, R01HL062052, R01AI20033, K08HL128809]
- Department of Medicine at the University of Rochester (NIAID grant) [RO1AI111914]
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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 amodel 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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