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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

Pathogenic effect of IL-22 in GVHD. Under physiological conditions, resident ILC3 cells take part in the intestinal microbiota and mucosal infiltrating lymphocyte homeostasis via IL-22 secretion. In this setting, IL-22 activity is controlled by IL-22BP produced by immature DC. In the allo-SCT setting, the conditioning regimen leads to epithelial barrier damage and host NK cell elimination. These lesions increase DAMP and PAMP secretion and induce pDC, neutrophil, and antigen-presenting cell infiltration, processes which activate donor T cells through the “cytokine storm.” Thus, IL-22 and type-I IFN take part in CXCL10 expression and induce Th1 inflammation.
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Figure 1: Pathogenic effect of IL-22 in GVHD. Under physiological conditions, resident ILC3 cells take part in the intestinal microbiota and mucosal infiltrating lymphocyte homeostasis via IL-22 secretion. In this setting, IL-22 activity is controlled by IL-22BP produced by immature DC. In the allo-SCT setting, the conditioning regimen leads to epithelial barrier damage and host NK cell elimination. These lesions increase DAMP and PAMP secretion and induce pDC, neutrophil, and antigen-presenting cell infiltration, processes which activate donor T cells through the “cytokine storm.” Thus, IL-22 and type-I IFN take part in CXCL10 expression and induce Th1 inflammation.

Mentions: The effect of IL-22 in allo-HSCT seems complex (Figure 1). Thymic RORγt+CCR6+NKp46−ILCs are crucial to secrete IL-22 that contributes to thymic regeneration after total body irradiation in mice (36). Post-transplantation IL-22 neutralization could have a direct impact on thymus regeneration and negatively influence immune reconstitution. The thymus regeneration seems more important during the first 2 weeks post-transplantation after IL-22 treatment, but after the second week, the size of the thymus is comparable to that of non-treated mice (69). However, a recent report showed that IL-22 administration to host mice is associated with a more severe intestinal GVHD. These data suggest that an increase in IL-22-dependent thymus regeneration is not correlated with less GVHD, but that IL-22 could be pathogenic for some tissues and protective for others in the same allogeneic context.


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)

Pathogenic effect of IL-22 in GVHD. Under physiological conditions, resident ILC3 cells take part in the intestinal microbiota and mucosal infiltrating lymphocyte homeostasis via IL-22 secretion. In this setting, IL-22 activity is controlled by IL-22BP produced by immature DC. In the allo-SCT setting, the conditioning regimen leads to epithelial barrier damage and host NK cell elimination. These lesions increase DAMP and PAMP secretion and induce pDC, neutrophil, and antigen-presenting cell infiltration, processes which activate donor T cells through the “cytokine storm.” Thus, IL-22 and type-I IFN take part in CXCL10 expression and induce Th1 inflammation.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Pathogenic effect of IL-22 in GVHD. Under physiological conditions, resident ILC3 cells take part in the intestinal microbiota and mucosal infiltrating lymphocyte homeostasis via IL-22 secretion. In this setting, IL-22 activity is controlled by IL-22BP produced by immature DC. In the allo-SCT setting, the conditioning regimen leads to epithelial barrier damage and host NK cell elimination. These lesions increase DAMP and PAMP secretion and induce pDC, neutrophil, and antigen-presenting cell infiltration, processes which activate donor T cells through the “cytokine storm.” Thus, IL-22 and type-I IFN take part in CXCL10 expression and induce Th1 inflammation.
Mentions: The effect of IL-22 in allo-HSCT seems complex (Figure 1). Thymic RORγt+CCR6+NKp46−ILCs are crucial to secrete IL-22 that contributes to thymic regeneration after total body irradiation in mice (36). Post-transplantation IL-22 neutralization could have a direct impact on thymus regeneration and negatively influence immune reconstitution. The thymus regeneration seems more important during the first 2 weeks post-transplantation after IL-22 treatment, but after the second week, the size of the thymus is comparable to that of non-treated mice (69). However, a recent report showed that IL-22 administration to host mice is associated with a more severe intestinal GVHD. These data suggest that an increase in IL-22-dependent thymus regeneration is not correlated with less GVHD, but that IL-22 could be pathogenic for some tissues and protective for others in the same allogeneic context.

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