Abstract 040: Cells of the Renin Lineage in the Peritoneal Cavity

Abstract

Renin cells have been traditionally associated with the control of blood pressure and fluid/electrolyte homeostasis. We recently described the presence of renin-expressing cells in the bone marrow, spleen and blood of mice. These cells are B-lymphocyte progenitors and show remarkable developmental, biochemical/transcriptional and functional similarities with the seemingly more distant kidney renin cell. While the function of these B renin cells within hematopoietic tissues remains unknown, we found that these progenitors are a vulnerable population for leukemic transformation: deletion of the Notch effector RBP-J within renin-expressing cells in mice leads to development of B-cell leukemia. Given their medical relevance, we sought to fully characterize the identity of renin cell descendants within the hematopoietic system. We generated Ren1 dcre/ + ; mT/mG mice which after Cre -mediated recombination express GFP in renin precursors and their descendants and then performed lineage tracing and transplantation studies. We found that cells from the renin lineage are enriched in the peritoneal fluid (12.3 +/- 1.7% at 4 months) when compared to bone marrow (1.2 +/- 0.02%), blood (2.6 +/- 0.72%) and spleen (5.3 +/- 0.4%). Further, while renin-expressing cells in the bone marrow are pro-B cells, cells from the renin lineage within the peritoneal fluid exhibit increased expression of CD11b and CD5, and overall have an immunophenotype consistent with B-1 lymphocytes. Whereas the proportion of cells from the renin lineage in bone marrow, blood, and spleen decreases with age, renin lineage B-1 cells within the peritoneal fluid persist into adulthood. Finally, we found that renin lineage cells from the bone marrow of donor mice can repopulate the B-1 cell peritoneal compartment in irradiated host mice. This preliminary work suggests an association between renin, the key regulatory enzyme of the renin angiotensin cascade and the innate immune system, two major systems in the control of homeostasis.