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Various forms of tissue damage and danger signals following hematopoietic stem-cell transplantation.

Ramadan A, Paczesny S - Front Immunol (2015)

Bottom Line: Alarmins, which are of endogenous origin, together with the exogenous pathogen-associated molecular patterns (PAMPs) elicit similar responses of danger signals and represent the group of damage-associated molecular patterns (DAMPs).Interestingly, some DAMPs and PAMPs are organ specific and GVHD-induced and have been shown to be interesting biomarkers.Some of these molecules may represent potential targets for novel therapeutic approaches.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Melvin and Bren Simon Cancer Center, Indiana University , Indianapolis, IN , USA ; Department of Microbiology and Immunology, Indiana University , Indianapolis, IN , USA.

ABSTRACT
Hematopoietic stem-cell transplantation (HSCT) is the most potent curative therapy for many malignant and non-malignant disorders. Unfortunately, a major complication of HSCT is graft-versus-host disease (GVHD), which is mediated by tissue damage resulting from the conditioning regimens before the transplantation and the alloreaction of dual immune components (activated donor T-cells and recipient's antigen-presenting cells). This tissue damage leads to the release of alarmins and the triggering of pathogen-recognition receptors that activate the innate immune system and subsequently the adaptive immune system. Alarmins, which are of endogenous origin, together with the exogenous pathogen-associated molecular patterns (PAMPs) elicit similar responses of danger signals and represent the group of damage-associated molecular patterns (DAMPs). Effector cells of innate and adaptive immunity that are activated by PAMPs or alarmins can secrete other alarmins and amplify the immune responses. These complex interactions and loops between alarmins and PAMPs are particularly potent at inducing and then aggravating the GVHD reaction. In this review, we highlight the role of these tissue damaging molecules and their signaling pathways. Interestingly, some DAMPs and PAMPs are organ specific and GVHD-induced and have been shown to be interesting biomarkers. Some of these molecules may represent potential targets for novel therapeutic approaches.

No MeSH data available.


Related in: MedlinePlus

Toll-like receptors and IL-1 receptor family signaling pathways. ST2L (IL-33r) and IL-1r signal through the MyD88, IRAK4, and TRAF6 pathway. ST2L and IL-1r share this pathway with most TLRs. Binding of ST2L, IL-1r, and TLRs activates NF-κb, resulting in the release of inflammatory cytokines. Most TLRs signal through MyD88 expect for TLR3, which signals through the TRIF pathway. TLR4 can signal through both MyD88 and TRIF. TLR3, TLR7/TLR8, and TLR9 are expressed in the endosome while other TLRs are expressed on the cell surface. TLR1 and TLR6 recognize their ligand with TLR2 heterodimers.
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Figure 2: Toll-like receptors and IL-1 receptor family signaling pathways. ST2L (IL-33r) and IL-1r signal through the MyD88, IRAK4, and TRAF6 pathway. ST2L and IL-1r share this pathway with most TLRs. Binding of ST2L, IL-1r, and TLRs activates NF-κb, resulting in the release of inflammatory cytokines. Most TLRs signal through MyD88 expect for TLR3, which signals through the TRIF pathway. TLR4 can signal through both MyD88 and TRIF. TLR3, TLR7/TLR8, and TLR9 are expressed in the endosome while other TLRs are expressed on the cell surface. TLR1 and TLR6 recognize their ligand with TLR2 heterodimers.

Mentions: Individual danger signaling pathways involved in GVHD are detailed below and summarized in Table 1. Figure 2 summarizes TLRs and IL-1 receptor family signaling pathways. Figure 3 summarizes PAMPs and DAMPs common pathogen recognition receptors and their interactions with the signaling pathways.


Various forms of tissue damage and danger signals following hematopoietic stem-cell transplantation.

Ramadan A, Paczesny S - Front Immunol (2015)

Toll-like receptors and IL-1 receptor family signaling pathways. ST2L (IL-33r) and IL-1r signal through the MyD88, IRAK4, and TRAF6 pathway. ST2L and IL-1r share this pathway with most TLRs. Binding of ST2L, IL-1r, and TLRs activates NF-κb, resulting in the release of inflammatory cytokines. Most TLRs signal through MyD88 expect for TLR3, which signals through the TRIF pathway. TLR4 can signal through both MyD88 and TRIF. TLR3, TLR7/TLR8, and TLR9 are expressed in the endosome while other TLRs are expressed on the cell surface. TLR1 and TLR6 recognize their ligand with TLR2 heterodimers.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4309199&req=5

Figure 2: Toll-like receptors and IL-1 receptor family signaling pathways. ST2L (IL-33r) and IL-1r signal through the MyD88, IRAK4, and TRAF6 pathway. ST2L and IL-1r share this pathway with most TLRs. Binding of ST2L, IL-1r, and TLRs activates NF-κb, resulting in the release of inflammatory cytokines. Most TLRs signal through MyD88 expect for TLR3, which signals through the TRIF pathway. TLR4 can signal through both MyD88 and TRIF. TLR3, TLR7/TLR8, and TLR9 are expressed in the endosome while other TLRs are expressed on the cell surface. TLR1 and TLR6 recognize their ligand with TLR2 heterodimers.
Mentions: Individual danger signaling pathways involved in GVHD are detailed below and summarized in Table 1. Figure 2 summarizes TLRs and IL-1 receptor family signaling pathways. Figure 3 summarizes PAMPs and DAMPs common pathogen recognition receptors and their interactions with the signaling pathways.

Bottom Line: Alarmins, which are of endogenous origin, together with the exogenous pathogen-associated molecular patterns (PAMPs) elicit similar responses of danger signals and represent the group of damage-associated molecular patterns (DAMPs).Interestingly, some DAMPs and PAMPs are organ specific and GVHD-induced and have been shown to be interesting biomarkers.Some of these molecules may represent potential targets for novel therapeutic approaches.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Melvin and Bren Simon Cancer Center, Indiana University , Indianapolis, IN , USA ; Department of Microbiology and Immunology, Indiana University , Indianapolis, IN , USA.

ABSTRACT
Hematopoietic stem-cell transplantation (HSCT) is the most potent curative therapy for many malignant and non-malignant disorders. Unfortunately, a major complication of HSCT is graft-versus-host disease (GVHD), which is mediated by tissue damage resulting from the conditioning regimens before the transplantation and the alloreaction of dual immune components (activated donor T-cells and recipient's antigen-presenting cells). This tissue damage leads to the release of alarmins and the triggering of pathogen-recognition receptors that activate the innate immune system and subsequently the adaptive immune system. Alarmins, which are of endogenous origin, together with the exogenous pathogen-associated molecular patterns (PAMPs) elicit similar responses of danger signals and represent the group of damage-associated molecular patterns (DAMPs). Effector cells of innate and adaptive immunity that are activated by PAMPs or alarmins can secrete other alarmins and amplify the immune responses. These complex interactions and loops between alarmins and PAMPs are particularly potent at inducing and then aggravating the GVHD reaction. In this review, we highlight the role of these tissue damaging molecules and their signaling pathways. Interestingly, some DAMPs and PAMPs are organ specific and GVHD-induced and have been shown to be interesting biomarkers. Some of these molecules may represent potential targets for novel therapeutic approaches.

No MeSH data available.


Related in: MedlinePlus