Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity

Taylor Eddens, Waleed Elsegeiny, Maria de la Luz Garcia-Hernadez, Patricia Castillo, Giraldina Trevejo-Nunez, Katelin Serody, Brian T. Campfield, Shabaana A. Khader, Kong Chen, Javier Rangel-Moreno, Jay K. Kolls

Research output: Contribution to journalArticle

21 Scopus citations

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.

Original languageEnglish
Pages (from-to)3078-3090
Number of pages13
JournalCell Reports
Volume18
Issue number13
DOIs
StatePublished - Mar 28 2017

Keywords

  • Cxcl13
  • Pneumocystis
  • Th17
  • Th2
  • fungus
  • iBALT
  • immunity
  • lymphoid tissue

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    Eddens, T., Elsegeiny, W., Garcia-Hernadez, M. D. L. L., Castillo, P., Trevejo-Nunez, G., Serody, K., Campfield, B. T., Khader, S. A., Chen, K., Rangel-Moreno, J., & Kolls, J. K. (2017). Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity. Cell Reports, 18(13), 3078-3090. https://doi.org/10.1016/j.celrep.2017.03.016