Meher, Akshaya
Primary Appointment
Assistant Professor of Research, Pharmacology
Education
- PhD, Protein Biochemistry and Biophysics, Central Drug Research Institute
Contact Information
Email: am5bv@virginia.edu
Research Disciplines
Molecular Pharmacology
Research Interests
Investigating the role of B cells in aortic aneurysm
Research Description
B-cell depletion therapy is widely used for treatment of cancers and autoimmune diseases. B cells are abundant in human abdominal aortic aneurysms (AAA); however, it is unknown whether B-cell depletion therapy affects AAA growth. We first developed a method to quantify B-cell subtypes in ~5mm segment of abdominal aorta collected from mice. We found that the number of both B1 and B2 cell was increased in AAA induced by elastase perfusion of abdominal aorta in wild-type mice. Next, we demonstrated that anti-CD20 antibody treatment significantly depleted B1 and B2 cells, and strikingly suppressed AAA growth in two experimental models of murine AAA. B-cell depletion resulted in lower circulating IgM levels, but did not affect the levels of IgG or cytokine/chemokine levels. Although the total number of leukocyte remained unchanged in elastase-perfused aortas after anti-CD20 antibody treatment, the number of B-cell subtypes was significantly lower. Interestingly, plasmacytoid dendritic cells expressing the immunomodulatory enzyme indole 2,3-dioxygenase were detected in the aortas of B-cell-depleted mice. In accordance with an increase in indole 2,3-dioxygenase+ plasmacytoid dendritic cells, the number of regulatory T cells was higher, whereas the expression of proinflammatory genes was lower in aortas of B-cell-depleted mice. In a coculture model, the presence of B cells significantly lowered the number of indole 2,3-dioxygenase+ plasmacytoid dendritic cells without affecting total plasmacytoid dendritic cell number. These results demonstrate that B-cell depletion protects mice from experimental AAA formation and promotes emergence of an immunosuppressive environment in aorta. Furthermore, our results suggest that B cell promote AAA growth. We are currently investigating how B cells promote AAA growth, which is funded by the national scientist development grant from American Heart Association.