Lymphocytes at the Heart of Wound Healing

Abstract

The adult mammalian heart displays negligible regenerative capacity. Therefore, myocardial infarction (MI) often results in an irreversible loss of contractile tissue, leading to a collagenous scar formation, progressive remodelling and heart failure (HF). Over the past few years, emerging evidences indicate that a myocardial ischemic injury mobilizes not only sterile unspecific inflammation but also lymphocyte-mediated immune responses to cardiac auto-antigens. In the current chapter, we depict the infarcted heart as a "wounded" tissue and focus on the dynamic events leading to myocardial repair, with special emphasis on the role played by lymphocytes in this process.

Persistent anti-heart autoimmunity causes cardiomyocyte damage in chronic heart failure

“…1) Persistent reactivity of heart-draining lymph nodes during CHF. An MI is a potent trigger for an acute local innate immune reaction, including early infiltration of neutrophils and macrophages (11) (11), but evidence is accumulating that T and B cells are also activated within a week post-MI (12). To investigate the activation state of the adaptive immune system in CHF progression, myocardial infarcts were induced in male Sprague Dawley rats by surgical ligation of the left anterior descending (LAD) coronary artery.…”

Myocardial infarction triggers cardioprotective antigen-specific T helper cell responses

“…Emerging concepts in the field of cardiology suggest that the infarcted myocardium could be perceived as a wounded tissue (46), and hence the immunological phenomena underlying myocardial repair have received considerable attention worldwide (5,8,(47)(48)(49)(50)(51). The contribution of innate immune mechanisms to post-MI inflammation, healing, and remodeling has been well scrutinized over the past 2 decades (52,53), but the involvement of the adaptive arm of the immune system has only recently been recognized (8,16,18,20,22,54,55). In this study, we assessed global features of the post-MI T cell repertoire and pinpointed a defined cardiac antigen that is targeted by CD4 + T cells after EMI to dissect the bidirectional cardio-immune crosstalk in unprecedented detail.…”

“…In fact, prospectively validated biomarkers are currently not available for monitoring the quality of ongoing myocardial healing, and thus clinicians cannot identify patients undergoing adverse remodeling until they reach a critical HF stage. Hence, there is an unmet need in the field of cardiology to better understand and eventually modulate the mechanisms underlying the myocardial repair process (8,67). A new discipline at the crossroads between immunology and cardiology has rapidly flourished over the past decade, with the aim of filling these gaps.…”

“…Cardiology and immunology are disciplines born apart, with different goals and tenets. Nonetheless, a fertile association between these areas of knowledge has recently flourished, and leukocytes have now been implicated in the control of cardiac metabolism (1), rhythm (2,3), aging (4), and repair (5)(6)(7)(8). The contribution of immunological phenomena to cardiac repair is of particular clinical relevance, because myocardial infarction (MI) is the leading cause of death worldwide (9).…”

Myocardial infarction does not affect circulating haematopoietic stem and progenitor cell self‐renewal ability in a rat model

“…The decreased percentage of lymphocytes at day 14 in the IG might be attributable to the post-infarction cardiac impairment that triggered important autonomic reflexes (e.g. sympathetic overdrive) and could also impact the physiology of lymphocytes in a non-classical fashion (Nunes-Silva et al 2017). Within groups, the significant increase in numbers of mature neutrophils and monocytes, but unchanged differentiation of immature HPCs (numbers of CFU-GMs) could imply disease- (Gentek & Hoeffel, 2017) or non-disease-related inflammation (Selig & Nothdurft, 1995).…”