The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?

Transplantation (Tx) remains the optimal therapy for end-stage disease (ESD) of various solid organs. Although alloimmune events remain the leading cause of long-term allograft loss, many patients develop innate and adaptive immune responses leading to graft tolerance. The focus of this review is to...

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Autores principales:	Mepur H. Ravindranath, Fatiha El Hilali, Edward J. Filippone
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	inflammation tolerance rejection allograft endothelial cells exosomes Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/eb4d6d66e3a445ce89eb19f61ecec5d6
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spelling	oai:doaj.org-article:eb4d6d66e3a445ce89eb19f61ecec5d62021-11-22T12:18:29ZThe Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?1664-322410.3389/fimmu.2021.667834https://doaj.org/article/eb4d6d66e3a445ce89eb19f61ecec5d62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.667834/fullhttps://doaj.org/toc/1664-3224Transplantation (Tx) remains the optimal therapy for end-stage disease (ESD) of various solid organs. Although alloimmune events remain the leading cause of long-term allograft loss, many patients develop innate and adaptive immune responses leading to graft tolerance. The focus of this review is to provide an overview of selected aspects of the effects of inflammation on this delicate balance following solid organ transplantation. Initially, we discuss the inflammatory mediators detectable in an ESD patient. Then, the specific inflammatory mediators found post-Tx are elucidated. We examine the reciprocal relationship between donor-derived passenger leukocytes (PLs) and those of the recipient, with additional emphasis on extracellular vesicles, specifically exosomes, and we examine their role in determining the balance between tolerance and rejection. The concept of recipient antigen-presenting cell “cross-dressing” by donor exosomes is detailed. Immunological consequences of the changes undergone by cell surface antigens, including HLA molecules in donor and host immune cells activated by proinflammatory cytokines, are examined. Inflammation-mediated donor endothelial cell (EC) activation is discussed along with the effect of donor-recipient EC chimerism. Finally, as an example of a specific inflammatory mediator, a detailed analysis is provided on the dynamic role of Interleukin-6 (IL-6) and its receptor post-Tx, especially given the potential for therapeutic interdiction of this axis with monoclonal antibodies. We aim to provide a holistic as well as a reductionist perspective of the inflammation-impacted immune events that precede and follow Tx. The objective is to differentiate tolerogenic inflammation from that enhancing rejection, for potential therapeutic modifications. (Words 247).Mepur H. RavindranathMepur H. RavindranathFatiha El HilaliEdward J. FilipponeFrontiers Media S.A.articleinflammationtolerancerejectionallograftendothelial cellsexosomesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	inflammation tolerance rejection allograft endothelial cells exosomes Immunologic diseases. Allergy RC581-607
spellingShingle	inflammation tolerance rejection allograft endothelial cells exosomes Immunologic diseases. Allergy RC581-607 Mepur H. Ravindranath Mepur H. Ravindranath Fatiha El Hilali Edward J. Filippone The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?
description	Transplantation (Tx) remains the optimal therapy for end-stage disease (ESD) of various solid organs. Although alloimmune events remain the leading cause of long-term allograft loss, many patients develop innate and adaptive immune responses leading to graft tolerance. The focus of this review is to provide an overview of selected aspects of the effects of inflammation on this delicate balance following solid organ transplantation. Initially, we discuss the inflammatory mediators detectable in an ESD patient. Then, the specific inflammatory mediators found post-Tx are elucidated. We examine the reciprocal relationship between donor-derived passenger leukocytes (PLs) and those of the recipient, with additional emphasis on extracellular vesicles, specifically exosomes, and we examine their role in determining the balance between tolerance and rejection. The concept of recipient antigen-presenting cell “cross-dressing” by donor exosomes is detailed. Immunological consequences of the changes undergone by cell surface antigens, including HLA molecules in donor and host immune cells activated by proinflammatory cytokines, are examined. Inflammation-mediated donor endothelial cell (EC) activation is discussed along with the effect of donor-recipient EC chimerism. Finally, as an example of a specific inflammatory mediator, a detailed analysis is provided on the dynamic role of Interleukin-6 (IL-6) and its receptor post-Tx, especially given the potential for therapeutic interdiction of this axis with monoclonal antibodies. We aim to provide a holistic as well as a reductionist perspective of the inflammation-impacted immune events that precede and follow Tx. The objective is to differentiate tolerogenic inflammation from that enhancing rejection, for potential therapeutic modifications. (Words 247).
format	article
author	Mepur H. Ravindranath Mepur H. Ravindranath Fatiha El Hilali Edward J. Filippone
author_facet	Mepur H. Ravindranath Mepur H. Ravindranath Fatiha El Hilali Edward J. Filippone
author_sort	Mepur H. Ravindranath
title	The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?
title_short	The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?
title_full	The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?
title_fullStr	The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?
title_full_unstemmed	The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?
title_sort	impact of inflammation on the immune responses to transplantation: tolerance or rejection?
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/eb4d6d66e3a445ce89eb19f61ecec5d6
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The Impact of Inflammation on the Immune Responses to Transplantation: Tolerance or Rejection?

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