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Interleukin-22 in Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation.

Lamarthée B, Malard F, Saas P, Mohty M, Gaugler B - Front Immunol (2016)

Bottom Line: Because of the lower toxicity of reduced intensity conditioning, the number of transplants is in constant increase.Acute GVHD is an exacerbated inflammatory response that leads to the destruction of healthy host tissues by donor immune cells.Interleukin-22 (IL-22) is produced by both immune and adaptive cells and has both protective and inflammatory properties.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche Saint Antoine, INSERM UMR 938, Paris, France; Université Pierre et Marie Curie, Paris, France.

ABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for hematologic malignancies and non-malignant diseases. Because of the lower toxicity of reduced intensity conditioning, the number of transplants is in constant increase. However, allo-HSCT is still limited by complications, such as graft-versus-host disease (GVHD), which is associated with important morbidity and mortality. Acute GVHD is an exacerbated inflammatory response that leads to the destruction of healthy host tissues by donor immune cells. Recently, the contribution of innate immunity in GVHD triggering has been investigated by several groups and resulted in the identification of new cellular and molecular effectors involved in GVHD pathogenesis. Interleukin-22 (IL-22) is produced by both immune and adaptive cells and has both protective and inflammatory properties. Its role in GVHD processes has been investigated, and the data suggest that its effect depends on the timing, the target tissue, and the origin of the producing cells (donor/host). In this review, we discuss the role of IL-22 in allo-HSCT and GVHD.

No MeSH data available.


Related in: MedlinePlus

STAT1 in intestinal inflammation. In response to PAMPs and DAMPs, pDCs (green cells) infiltrate intestinal tissues and secrete type-I IFN after TLR activation and STAT1 phosphorylation. Type-I IFN induces STAT1 activation in intestinal epithelial cells (pink cells), leading to local CXCL10 expression. CXCL10 induces CXCR3+ T cell (blue cells) recruitment and their differentiation into Th1, able to produce type-II IFN under STAT1 dependence. Thus, Th1 cells participate in local inflammation and also secrete IL-22 that contributes to STAT1 activation in IEC.
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Figure 2: STAT1 in intestinal inflammation. In response to PAMPs and DAMPs, pDCs (green cells) infiltrate intestinal tissues and secrete type-I IFN after TLR activation and STAT1 phosphorylation. Type-I IFN induces STAT1 activation in intestinal epithelial cells (pink cells), leading to local CXCL10 expression. CXCL10 induces CXCR3+ T cell (blue cells) recruitment and their differentiation into Th1, able to produce type-II IFN under STAT1 dependence. Thus, Th1 cells participate in local inflammation and also secrete IL-22 that contributes to STAT1 activation in IEC.

Mentions: Paradoxically, donor-derived IL-22 aggravates intestinal damage during GVHD (66). It has been recently reported that IL-22BP expression is maximal when the intestinal barrier is preserved (42). Conversely, tissue lesions and bacterial translocation decrease IL-22BP expression. The mechanism underlying the expression of IL-22BP by DC is inflammasome dependent (94). Thus, IL-18 can inhibit IL-22BP expression by DC (95). In the GVHD context, the contribution of IL-18 remains controversial (96, 97). Nevertheless, Munoz and colleagues recently described an important property of this cytokine. They showed that IL-22 maintains homeostatic IL-18 expression in epithelial cells and IL-8 can be augmented during infection. Moreover, active IL-18 is responsible for a unique inflammatory feedback loop to amplify Th1 cell-mediated immune response (98). Whether donor-derived IL-22 can amplify Th1 response through IL-18 secretion in the GVHD context remains to be addressed (Figure 2). The decrease of IL-22BP expression probably increases bioactive IL-22 at local level. These observations should be confirmed in allo-HSCT patients. Interestingly, antimicrobial peptides, such as Reg3α, that are produced by Paneth cells in response to IL-22 are detected in the blood of GVHD patients and have been validated as intestinal GVHD biomarkers (99). These data are in line with Eriguchi’s group observations, which showed an increase of defensin expression in GVHD mice, which confirm that IL-22 is well active in intestinal tissue during allo-HSCT (66, 100).


Interleukin-22 in Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation.

Lamarthée B, Malard F, Saas P, Mohty M, Gaugler B - Front Immunol (2016)

STAT1 in intestinal inflammation. In response to PAMPs and DAMPs, pDCs (green cells) infiltrate intestinal tissues and secrete type-I IFN after TLR activation and STAT1 phosphorylation. Type-I IFN induces STAT1 activation in intestinal epithelial cells (pink cells), leading to local CXCL10 expression. CXCL10 induces CXCR3+ T cell (blue cells) recruitment and their differentiation into Th1, able to produce type-II IFN under STAT1 dependence. Thus, Th1 cells participate in local inflammation and also secrete IL-22 that contributes to STAT1 activation in IEC.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836046&req=5

Figure 2: STAT1 in intestinal inflammation. In response to PAMPs and DAMPs, pDCs (green cells) infiltrate intestinal tissues and secrete type-I IFN after TLR activation and STAT1 phosphorylation. Type-I IFN induces STAT1 activation in intestinal epithelial cells (pink cells), leading to local CXCL10 expression. CXCL10 induces CXCR3+ T cell (blue cells) recruitment and their differentiation into Th1, able to produce type-II IFN under STAT1 dependence. Thus, Th1 cells participate in local inflammation and also secrete IL-22 that contributes to STAT1 activation in IEC.
Mentions: Paradoxically, donor-derived IL-22 aggravates intestinal damage during GVHD (66). It has been recently reported that IL-22BP expression is maximal when the intestinal barrier is preserved (42). Conversely, tissue lesions and bacterial translocation decrease IL-22BP expression. The mechanism underlying the expression of IL-22BP by DC is inflammasome dependent (94). Thus, IL-18 can inhibit IL-22BP expression by DC (95). In the GVHD context, the contribution of IL-18 remains controversial (96, 97). Nevertheless, Munoz and colleagues recently described an important property of this cytokine. They showed that IL-22 maintains homeostatic IL-18 expression in epithelial cells and IL-8 can be augmented during infection. Moreover, active IL-18 is responsible for a unique inflammatory feedback loop to amplify Th1 cell-mediated immune response (98). Whether donor-derived IL-22 can amplify Th1 response through IL-18 secretion in the GVHD context remains to be addressed (Figure 2). The decrease of IL-22BP expression probably increases bioactive IL-22 at local level. These observations should be confirmed in allo-HSCT patients. Interestingly, antimicrobial peptides, such as Reg3α, that are produced by Paneth cells in response to IL-22 are detected in the blood of GVHD patients and have been validated as intestinal GVHD biomarkers (99). These data are in line with Eriguchi’s group observations, which showed an increase of defensin expression in GVHD mice, which confirm that IL-22 is well active in intestinal tissue during allo-HSCT (66, 100).

Bottom Line: Because of the lower toxicity of reduced intensity conditioning, the number of transplants is in constant increase.Acute GVHD is an exacerbated inflammatory response that leads to the destruction of healthy host tissues by donor immune cells.Interleukin-22 (IL-22) is produced by both immune and adaptive cells and has both protective and inflammatory properties.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche Saint Antoine, INSERM UMR 938, Paris, France; Université Pierre et Marie Curie, Paris, France.

ABSTRACT
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential curative treatment for hematologic malignancies and non-malignant diseases. Because of the lower toxicity of reduced intensity conditioning, the number of transplants is in constant increase. However, allo-HSCT is still limited by complications, such as graft-versus-host disease (GVHD), which is associated with important morbidity and mortality. Acute GVHD is an exacerbated inflammatory response that leads to the destruction of healthy host tissues by donor immune cells. Recently, the contribution of innate immunity in GVHD triggering has been investigated by several groups and resulted in the identification of new cellular and molecular effectors involved in GVHD pathogenesis. Interleukin-22 (IL-22) is produced by both immune and adaptive cells and has both protective and inflammatory properties. Its role in GVHD processes has been investigated, and the data suggest that its effect depends on the timing, the target tissue, and the origin of the producing cells (donor/host). In this review, we discuss the role of IL-22 in allo-HSCT and GVHD.

No MeSH data available.


Related in: MedlinePlus