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Resolution of acute intestinal graft-versus-host disease

  • Sindhu Thiagarajan
  • Markus F. Neurath
  • Kai HildnerEmail author
Review

Abstract

Allogeneic transplantation of hematopoietic stem cells (allo-HCT) represents an increasingly employed therapeutic approach to potentially cure patients suffering from life-threatening malignant and autoimmune disorders. Despite its lifesaving potential, immune-mediated allo-reactivity inherent to the allogeneic transplantation can be observed within up to 50% of all allo-HCT patients regularly resulting in the manifestation of acute and/or chronic graft-versus-host disease (GvHD). Mechanistically, especially donor T cells are assumed to chiefly drive inflammation that can occur in virtually all organs, with the skin, liver, and gut representing as the most frequently affected anatomic sites. Especially in the presence of intestinal manifestations of GvHD, the risk that the disease takes a life-threatening, potentially fatal course is significantly increased. In the light of a rapid gain of knowledge in respect to decode innate and adaptive immunity related mechanisms as, e.g., cytokine networks, intracellular signaling pathways or environmental triggers as, e.g., the intestinal microbiota and the development of novel therapeutic approaches, detailed insight into endogenous mechanisms seeking to counterbalance the proinflammatory machinery or to proactively foster signals promoting the resolution of allo-driven intestinal inflammation is emerging. Here, we seek to highlight the key aspects of those mechanisms involved in and contributing to the resolution of GvHD-associated intestinal inflammation. Concomitantly, we would like to briefly outline and discuss promising future experimental targets suitable to be therapeutically employed to directionally deflect the tissue response from a proinflammatory to an inflammation-resolving type of intestinal GvHD after allo-HCT.

Keywords

Allogeneic hematopoietic stem cell transplantation Intestinal graft-versus-host disease T cells resolution of intestinal GvHD 

Notes

Funding information

This study was supported by the Collaborative Research Center 1181 (DFG-CRC1181, project B05), University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg (to K.H) and the Collaborative Research Center 221 (DFG-CRC221, project B03 [K.H.].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medicine 1, University Hospital ErlangenUniversity of Erlangen-Nuremberg, Kussmaul Campus for Medical ResearchErlangenGermany
  2. 2.University Hospital ErlangenDeutsches Zentrum Immuntherapie (DZI)ErlangenGermany

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