Allograft or Recipient ST2 Deficiency Oppositely Affected Cardiac Allograft Vasculopathy via Differentially Altering Immune Cells Infiltration.

Zhenggang Zhang,Junyu Shi,Yong Xu,Suo Wu,Yunfei Liu,Feili Gong,Mengya Jiao,Na Zhang,Fang Zheng,Zheng Tan,Xuhuan Tang,Xiaoxiao Li,Chan Dai

doi:10.3389/fimmu.2021.657803

Abstract

The role of IL-33/ST2 signaling in cardiac allograft vasculopathy (CAV) is not fully addressed. Here, we investigated the role of IL-33/ST2 signaling in allograft or recipient in CAV respectively using MHC-mismatch murine chronic cardiac allograft rejection model. We found that recipients ST2 deficiency significantly exacerbated allograft vascular occlusion and fibrosis, accompanied by increased F4/80+ macrophages and CD3+ T cells infiltration in allografts. In contrast, allografts ST2 deficiency resulted in decreased infiltration of F4/80+ macrophages, CD3+ T cells and CD20+ B cells and thus alleviated vascular occlusion and fibrosis of allografts. These findings indicated that allografts or recipients ST2 deficiency oppositely affected cardiac allograft vasculopathy/fibrosis via differentially altering immune cells infiltration, which suggest that interrupting IL-33/ST2 signaling locally or systematically after heart transplantation leads different outcome.

Highlights

Despite improvement in short-term patient survival after heart transplantation (HTx), long-term survival rates have not improved much, mainly because of Cardiac Allograft Vasculopathy (CAV) [1]
Compared with C57!bm12 group, deficiency of ST2 in cardiac allografts (ST2-/-!bm12 group) markedly alleviated the coronary arterial stenosis at week 4 and 8 (Figures 1A, right panel, B red line). These results suggested that the ST2 signaling in the recipient prevents, and in the transplanted heart enhance, the cardiac allograft vasculopathy
The aim of this study was to accurately address the role of IL-33/ST2 signaling in cardiac allograft vasculopathy via deleting ST2 in allograft or recipient respectively

Summary

Introduction

Despite improvement in short-term patient survival after heart transplantation (HTx), long-term survival rates have not improved much, mainly because of Cardiac Allograft Vasculopathy (CAV) [1]. CAV is a major cause of graft failure in cardiac transplant recipients who survives more than 1 year after transplantation, with the morbidity of CAV exceeding 50% at 5 years [2]. CAV is primarily characterized as an immune-mediated pan-arterial disease with intimal hyperplasia and narrowing of the allograft artery [3]. Recent insights have underscored the fact that innate and specific immune responses are involved in the pathogenesis of CAV [4, 5]. Past extensive studies, the molecular mechanisms underlying cardiac allograft vasculopathy are not yet to be fully elucidated [6]. IL-33 has been identified to be the special ligand

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