Immune Netw.  2017 Jun;17(3):144-151. 10.4110/in.2017.17.3.144.

TLR/MyD88-mediated Innate Immunity in Intestinal Graft-versus-Host Disease

• Lee YK
• Kang M
• Choi EY

• KMID: 2383352
• DOI: http://doi.org/10.4110/in.2017.17.3.144

Abstract

Graft-versus-host disease (GHVD) is a severe complication after allogeneic hematopoietic stem cell transplantation. The degree of inflammation in the gastrointestinal tract, a major GVHD target organ, correlates with the disease severity. Intestinal inflammation is initiated by epithelial damage caused by pre-conditioning irradiation. In combination with damages caused by donor-derived T cells, such damage disrupts the epithelial barrier and exposes innate immune cells to pathogenic and commensal intestinal bacteria, which release ligands for Toll-like receptors (TLRs). Dysbiosis of intestinal microbiota and signaling through the TLR/myeloid differentiation primary response gene 88 (MyD88) pathways contribute to the development of intestinal GVHD. Understanding the changes in the microbial flora and the roles of TLR signaling in intestinal GVHD will facilitate the development of preventative and therapeutic strategies.

Keyword

Graft-versus-host disease; Innate immune response; Toll-like receptor; MyD88; Myeloid derived suppressor cells (MDSCs)

MeSH Terms

Bacteria
Dysbiosis
Gastrointestinal Microbiome
Gastrointestinal Tract
Graft vs Host Disease*
Hematopoietic Stem Cell Transplantation
Immunity, Innate*
Inflammation
Ligands
T-Lymphocytes
Toll-Like Receptors
Ligands
Toll-Like Receptors

Figure

• 

  Figure 1 Schematic diagram of the development of acute GVHD. Acute GVHD can be classified into five distinct phases. Conditioning regimens (radiation or chemotherapy) induce tissue damage (I), and increase production of inflammatory cytokines, which cause the activation and maturation of APCs (II), leading to allo-reactive donor T cell priming and expansion (III). Activated donor T cells migrate to damaged host tissues (IV), where they amplify inflammatory responses and worsen GVHD (V). DC, dendritic cell; MΦ, macrophage.

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