Journal Article

Macrophages promote polycystic kidney disease progression

Swenson-Fields, Katherine I, Davis, Bradley M, Fields, Timothy A, Vivian, Carolyn J, Peda, Jacqueline D, Salah, Sally M, van Rooijen, Nico, Wallace, Darren P

2013

Overview

Renal M2-like macrophages have critical roles in tissue repair, stimulating tubule cell proliferation and, if they remain, fibrosis. M2-like macrophages have also been implicated in promoting cyst expansion in mouse models of autosomal dominant polycystic kidney disease (ADPKD). While renal macrophages have been documented in human ADPKD, there are no studies in autosomal recessive polycystic kidney disease (ARPKD). Here we evaluated the specific phenotype of renal macrophages and their disease-impacting effects on cystic epithelial cells. We found an abundance of M2-like macrophages in the kidneys of patients with either ADPKD or ARPKD and in the cystic kidneys of cpk mice, a model of ARPKD. Renal epithelial cells from either human ADPKD cysts or noncystic human kidneys promote differentiation of naive macrophages to a distinct M2-like phenotype in culture. Reciprocally, these immune cells stimulate the proliferation of renal tubule cells and microcyst formation in vitro. Further, depletion of macrophages from cpk mice indicated that macrophages contribute to PKD progression regardless of the genetic etiology. Thus, M2-like macrophages are two-pronged progression factors in PKD, promoting cyst cell proliferation, cyst growth, and fibrosis. Agents that block the emergence of these cells or their effects in the cystic kidney may be effective therapies for slowing PKD progression.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Animals / Cell Proliferation / Cells, Cultured / clodronate / Coculture Techniques / Disease Models, Animal / Disease Progression / Epithelial Cells - immunology / Epithelial Cells - metabolism / Epithelial Cells - pathology / Fibrosis / Humans / Kidney - immunology / Kidney - metabolism / Kidney - pathology / M2 macrophage / Macrophages - immunology / Macrophages - metabolism / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Paracrine Communication / Phenotype / polycystic kidney disease / Polycystic Kidney, Autosomal Dominant - genetics / Polycystic Kidney, Autosomal Dominant - immunology / Polycystic Kidney, Autosomal Dominant - metabolism / Polycystic Kidney, Autosomal Dominant - pathology / Polycystic Kidney, Autosomal Recessive - genetics / Polycystic Kidney, Autosomal Recessive - immunology / Polycystic Kidney, Autosomal Recessive - metabolism / Polycystic Kidney, Autosomal Recessive - pathology