A novel role for IL-22R1 as a driver of inflammation

Abstract

The interleukin (IL)-22R1 chain of the heterodimeric IL-22 receptor is not expressed on normal leukocytes, but this receptor is expressed on T cells from anaplastic lymphoma kinase-positive (ALK ؉ ) anaplastic large cell lymphoma (ALCL) patients. To investigate the consequences of aberrant expression of this receptor on lymphocytes, we generated transgenic mice that express IL-22R1 on lymphocytes. The health of these animals progressively deteriorated at 8 to 12 weeks of age, as they displayed respiratory distress, rough coat and sluggish movement, and subsequent lethality due to multiorgan inflammation. The IL-22R1 transgenic animals developed neutrophilia that correlated with increased levels of circulating IL-17 and granulocyte colony-stimulating factor. In addition, these mice had increased serum

Expression of mRNA for IL-22 Binding Protein in the Broncheoalveolar Fluid after Inhaled Allergen Challenge in Subjects with Asthma

“…In vitro, we could induce mRNA expression for IL-22 BP in PBMCs from individuals with atopic asthma and healthy controls after co-incubation with the Th2 cytokine IL-4. In accordance with others, we found continuous mRNA expression for IL-22 -and not for the both receptor chains -in PMCs and mononuclear cells of the BALF [15,20].…”

ALK+ALCLs induce cutaneous, HMGB-1–dependent IL-8/CXCL8 production by keratinocytes through NF-κB activation

“…4 The subsequent release of cytokines leading to skin inflammation at the site of the bite could act as a "second hit" eliciting activation of T lymphocytes, which would then express the oncogenic NPM-ALK protein and undergo uncontrolled proliferation and transformation. 4 ALK ϩ ALCL patients also present with an inflammatory syndrome characterized by high fever, lymphadenopathy or neutrophilia, release of various circulating inflammatory chemokines such as IL-8, 5 and expression of skin-inflammatory biomarkers such as the alarmins heat-shock protein 90 (HSP90), HSP70, 6 S100A8, or A11. 7 Recent studies have highlighted a role for IL-8 in mediating cutaneous skin inflammation and human keratinocyte hyperplasia associated with acanthosis (thickening of the skin).…”

Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis-associated anaplastic large cell lymphoma in children

“…These situations are probably related to the activation of the immune system by a massive liberation of cytokines especially IL4, IL13 and TNFa, and to an over expression of IL22R1 on lymphocytes (Savan et al, 2011;Mellgren et al, 2012). Some of these situations probably fit the diagnosis criteria of HLH even though the presence of a HLH has rarely been described in children with ALCL, with only nine cases (Table V) reported in the literature (Blatt et al, 2002;Han et al, 2007;Krenova et al, 2007;Sevilla et al, 2007;Shimada et al, 2008; …”