TY - JOUR
T1 - THE CARDIOSPLENIC AXIS IS ESSENTIAL FOR THE PATHOGENESIS OF ISCHEMIC HEART FAILURE
AU - Prabhu, Sumanth D.
PY - 2018
Y1 - 2018
N2 - The role of innate and adaptive immunity in heart failure (HF) is poorly understood. We discovered that mice with ischemic HF exhibit robust expansion of proinflammatory monocytes/macrophages, classical and plasmacytoid dendritic cells, and CD4+ and CD8+ T cells. There was profound splenic remodeling indicative of heightened antigen processing, and expanded antigen-experienced effector and memory CD4+ T cell populations. A series of subsequent studies in HF mice that incorporated splenectomy, adoptive transfer of both unselected splenocytes and splenic CD4+ T-cells, and antibody-mediated CD4+ T-cell depletion indicated that intensely activated splenic immune cells: 1) underlie the chronic inflammatory response in HF, 2) traffic and home to the failing heart, and 3) exhibit immune memory and are primed to induce tissue injury that promotes pathological cardiac remodeling. Hence, we propose that ischemic cardiomyopathy is in part an immune-mediated disease, against as-of-yet unidentified cardiac antigens, with a central role for the spleen in this process.
AB - The role of innate and adaptive immunity in heart failure (HF) is poorly understood. We discovered that mice with ischemic HF exhibit robust expansion of proinflammatory monocytes/macrophages, classical and plasmacytoid dendritic cells, and CD4+ and CD8+ T cells. There was profound splenic remodeling indicative of heightened antigen processing, and expanded antigen-experienced effector and memory CD4+ T cell populations. A series of subsequent studies in HF mice that incorporated splenectomy, adoptive transfer of both unselected splenocytes and splenic CD4+ T-cells, and antibody-mediated CD4+ T-cell depletion indicated that intensely activated splenic immune cells: 1) underlie the chronic inflammatory response in HF, 2) traffic and home to the failing heart, and 3) exhibit immune memory and are primed to induce tissue injury that promotes pathological cardiac remodeling. Hence, we propose that ischemic cardiomyopathy is in part an immune-mediated disease, against as-of-yet unidentified cardiac antigens, with a central role for the spleen in this process.
UR - http://www.scopus.com/inward/record.url?scp=85059796119&partnerID=8YFLogxK
M3 - Article
C2 - 30166715
AN - SCOPUS:85059796119
SN - 0065-7778
VL - 129
SP - 202
EP - 214
JO - Transactions of the American Clinical and Climatological Association
JF - Transactions of the American Clinical and Climatological Association
ER -