Therapeutic opportunities of the IL-22–IL-22R1 system

Sabat, Robert; Ouyang, Wenjun; Wolk, Kerstin

doi:10.1038/nrd4176

Cited by 476 publications

(511 citation statements)

References 170 publications

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“…Thereby, NCR + ILC3 suppress further tissue damage, alloreactive T cell activation and the occurrence of GVHD (Figure 2) 31. Furthermore, IL‐22 cytokine‐based therapy has already been considered for prevention of GVHD and lung transplantation complications 37. The active status and gut/skin homing receptor expression of ILC, especially the IL‐22‐producing ILC3, seems to minimize GVHD development following HCT.…”

Section: Potential Of Il‐22 Producing Ilc3 In Gvhd Therapymentioning

confidence: 99%

“…IL‐22 could be a relatively safe target in enhancing mucosal healing, since it does not directly affect immune cell functions. However, possible adverse effects might occur, for example, due to dysregulated responses of keratinocytes in the skin 20, 37. Of note, in an earlier large‐scale clinical study investigating human gastrointestinal GVHD risk factors, Reg3α protein was identified as indicator of higher incidence for developing GVHD after allo‐HCT 38.…”

Section: Potential Of Il‐22 Producing Ilc3 In Gvhd Therapymentioning

confidence: 99%

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Innate Lymphoid Cells in Graft-Versus-Host Disease

Kónya

Mjösberg

2015

American Journal of Transplantation

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Innate lymphoid cells (ILC) are lymphocytes lacking rearranged antigen receptors such as those expressed by T and B cells. ILC are important effector and regulatory cells of the innate immune system, controlling lymphoid organogenesis, tissue inflammation, and homeostasis. The family of ILC consists of cytotoxic NK cells and the more recently described noncytotoxic group 1, 2, and 3 ILC. The classification of noncytotoxic ILC—in many aspects—mirrors that of T helper cells, which is based on the expression of master transcription factors and signature cytokines specific for each subset. The IL‐22 producing RORγt+ ILC3 subset was recently found to be critical in the prevention of intestinal graft‐versus‐host disease (GVHD) following allogeneic hematopoietic cell transplantation (HCT) via strengthening the intestinal mucosal barrier. In this review, we summarize the current view of the immunological functions of human noncytotoxic ILC subsets and discuss the potentially beneficial features of IL‐22 producing ILC3 in improving allo‐HCT efficacy by attenuating susceptibility to GVHD. In addition, we explore the possibility of other ILC subsets playing a role in GVHD.

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Section: Potential Of Il‐22 Producing Ilc3 In Gvhd Therapymentioning

confidence: 99%

Section: Potential Of Il‐22 Producing Ilc3 In Gvhd Therapymentioning

confidence: 99%

Innate Lymphoid Cells in Graft-Versus-Host Disease

Kónya

Mjösberg

2015

American Journal of Transplantation

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“…ILC3s are a group of lymphocytes without T‐cell‐specific antigen receptors with particular accumulation at mucosal sites and serve as key regulators during intestinal inflammation 18, 19, 20, 21. ILC3s can rapidly respond to external stimuli and play critical roles in host defense, the resolution of inflammation and initiation of tissue repair in the gut 21, 22, 23, 24, 25, 26. These protective effects of ILC3s are mostly dependent on their production of the reparative cytokine IL‐22.…”

Section: Introductionmentioning

confidence: 99%

“…These protective effects of ILC3s are mostly dependent on their production of the reparative cytokine IL‐22. By binding to its receptor on epithelial cells, IL‐22 contributes to production of antimicrobial peptides and mucins, regulation of gut microbiota, maintenance of the gut barrier function and amelioration of intestinal inflammation 25, 26. But it remains unclear how ILC3s are activated and regulated during intestinal inflammation.…”

Section: Introductionmentioning

confidence: 99%

Purine metabolism controls innate lymphoid cell function and protects against intestinal injury

et al. 2018

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Inflammatory bowel disease (IBD) is a condition of chronic inflammatory intestinal disorder with increasing prevalence but limited effective therapies. The purine metabolic pathway is involved in various inflammatory processes including IBD. However, the mechanisms through which purine metabolism modulates IBD remain to be established. Here, we found that mucosal expression of genes involved in the purine metabolic pathway is altered in patients with active ulcerative colitis (UC), which is associated with elevated gene expression signatures of the group 3 innate lymphoid cell (ILC3)–interleukin (IL)‐22 pathway. In mice, blockade of ectonucleotidases (NTPDases), critical enzymes for purine metabolism by hydrolysis of extracellular adenosine 5′‐triphosphate (eATP) into adenosine, exacerbates dextran‐sulfate sodium‐induced intestinal injury. This exacerbation of colitis is associated with reduction of colonic IL‐22‐producing ILC3s, which afford essential protection against intestinal inflammation, and is rescued by exogenous IL‐22. Mechanistically, activation of ILC3s for IL‐22 production is reciprocally mediated by eATP and adenosine. These findings reveal that the NTPDase‐mediated balance between eATP and adenosine regulates ILC3 cell function to provide protection against intestinal injury and suggest potential therapeutic strategies for treating IBD by targeting the purine–ILC3 axis.

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“…Interleukin-22 has been the focus of emerging research in a variety of systemic inflammatory diseases and it has been identified as a key regulator of host defense acting directly at the mucosal barriers [10,11]. Little is known about IL-22 and reproductive function.…”

Section: Introductionmentioning

confidence: 99%

Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss

Perfetto

Fan

Dahl

et al. 2015

J Assist Reprod Genet

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Purpose Researchers have hypothesized that an imbalance of immune cells in the uterine decidua and a dysfunction in cytokines they produce may contribute to recurrent pregnancy loss (RPL). The objective of this study was to determine if IL-22, IL-23 and IL-17 are expressed abnormally in the decidua of patients with RPL compared to those women with a normal pregnancy. We also sought to confirm that uterine natural killer (uNK) cells are lower in the decidua of patients with RPL, as well as identify IL-22 expression by uNK cells. Methods After meeting strict inclusion criteria, maternal decidua of nine patients with unexplained RPL and a confirmed euploid fetal loss, and 11 gestational age-matched patients undergoing elective pregnancy termination were included in our analysis. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to quantify RNA expression, Western blot was performed to quantify protein expression and immunohistochemistry (IHC) was performed to identify IL-22 and uNK cells. Results We found that women with unexplained RPL and a euploid fetal loss had significantly less gene and protein expression of IL-22 in the decidua. Additionally, we found that IL-22 is primarily expressed by uNK cells in the decidua. Conclusions In conclusion, our results suggest that lower levels of IL-22 in the uterine decidua in patients with unexplained RPL may contribute to a disruption of decidual homeostasis and ultimately lead to early pregnancy loss.

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Therapeutic opportunities of the IL-22–IL-22R1 system

Cited by 476 publications

References 170 publications

Innate Lymphoid Cells in Graft-Versus-Host Disease

Innate Lymphoid Cells in Graft-Versus-Host Disease

Purine metabolism controls innate lymphoid cell function and protects against intestinal injury

Expression of interleukin-22 in decidua of patients with early pregnancy and unexplained recurrent pregnancy loss

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