MBI 501 Graduate Student Seminar
Thursday, May 16, 2013
K-207 (Room 2-6408)
Presenter: Ji Young Hwang Advisor: Dr. Troy D. Randall
Inducible bronchus-associated lymphoid tissue (iBALT) reduces Th2-driven
pathology by redistributing leukocytes within the lung
Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic lymphoid tissue formed in the lung after pulmonary infection or inflammation. This local lymphoid tissue is structurally similar to conventional secondary lymphoid organs, with separated B and T cell areas, specialized stromal cells and lymphoid dendritic cells (DCs). Here, we tested whether the presence of iBALT affects pulmonary immune responses to allergens. We induced iBALT formation in neonatal mice by pulmonary administration of LPS, and when the mice were adults, sensitized and challenged them intranasally with OVA. We found that mice with iBALT had fewer eosinophils, less goblet cells and had reduced Th2 cytokine production in bronchoalveolar (BAL) fluid and lung tissue after OVA challenge. Although the differences were not always significant, they had a tendency to decrease after iBALT was induced. Surprisingly, using IL-4 reporter and by transferring OVA-specific OT-II cells, we found that the presence of iBALT did not reduce the number of Th2 cells that accumulated in the lung. Despite similar numbers of Th2 effectors in the lungs of mice with and without iBALT, we found that Th2 cells were differentially distributed in these two groups of mice. Those in the lungs of mice without iBALT were more widely dispersed, whereas the cells in the lungs of mice with iBALT were predominantly concentrated in the lymphoid tissue. These results suggest that the reduction in Th2-driven pathology with iBALT is due to the redistribution of leukocytes within the lung after iBALT formation.
Although inducing iBALT by chronic inflammation-like responses with LPS is a useful tool, one of the issues with LPS is that we do not know what LPS is doing other than inducing iBALT. To understand the role of iBALT in allergic airway diseases independently of LPS, we are generating a transgenic mouse by which, an overexpression of a homeostatic chemokine, CXCL13, specifically in the lung will initiate the lymphoid neogenesis using doxycycline. This will allow us to regulate the induction of the ectopic lymphoid tissue temporally as well as spatially.