IL-22 Administration Protects Intestinal Stem Cells from Gvhd

Lindemans, Caroline A.; Mertelsmann, Anna; Dudakov, Jarrod A; Velardi, Enrico; Hua, Guoqiang; O'Connor, Margaret; Kolesnick, Richard; Brink, Marcel R.M. van den; Hanash, Alan M.

doi:10.1016/j.bbmt.2013.12.056

Cited by 1 publication

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“…As mentioned before, IL-22-producing ILC3s have a crucial role in reducing epithelial and intestinal stem-cell damage and reducing GVHD severity and mortality ( 228 ). The same research group has demonstrated that daily administration of IL-22 for 3 weeks starting 1 week post-transplantation increases the survival and function of host radio-resistant ILC3s, subsequently reducing apoptosis in host intestinal stem cells and reducing GVHD severity through preservation of host cells from damage without compromising immune function or reconstitution ( 275 ). This makes IL-22 administration one of most promising therapies for GI GVHD.…”

Section: Therapeutic Approaches To Target Danger Signalsmentioning

confidence: 99%

Various Forms of Tissue Damage and Danger Signals Following Hematopoietic Stem-Cell Transplantation

Ramadan

Paczesny

2015

Front. Immunol.

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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.

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Section: Therapeutic Approaches To Target Danger Signalsmentioning

confidence: 99%