Distinct Expression Patterns of Interleukin-22 Receptor 1 on Blood Hematopoietic Cells in SARS-CoV-2 Infection

Abstract

The new pandemic virus SARS-CoV-2 is characterized by uncontrolled hyper-inflammation in severe cases. As the IL-22/IL-22R1 axis was reported to be involved in inflammation during viral infections, we characterized the expression of IL-22 receptor1, IL-22 and IL-22 binding protein in COVID-19 patients. Blood samples were collected from 19 non-severe and 14 severe patients on the day they presented (D0), at D14, and six months later, and from 6 non-infected controls. The IL-22R1 expression was characterized by flow cytometry. Results were related to HLA-DR expression of myeloid cells, to plasma concentrations of different cytokines and chemokines and NK cells and T lymphocytes functions characterized by their IFN-γ, IL-22, IL-17A, granzyme B and perforin content. The numbers of IL-22R1+ classical, intermediate, and non-classical monocytes and the proportions of IL-22R1+ plasmacytoid DC (pDC), myeloid DC1 and DC2 (mDC1, mDC2) were higher in patients than controls at D0. The proportions of IL-22R1+ classical and intermediate monocytes, and pDC and mDC2 remained high for six months. High proportions of IL-22R1+ non-classical monocytes and mDC2 displayed HLA-DRhigh expression and were thus activated. Multivariate analysis for all IL-22R1+ myeloid cells discriminated the severity of the disease (AUC=0.9023). However, correlation analysis between IL-22R1+ cell subsets and plasma chemokine concentrations suggested pro-inflammatory effects of some subsets and protective effects of others. The numbers of IL-22R1+ classical monocytes and pDC were positively correlated with pro-inflammatory chemokines MCP-1 and IP-10 in severe infections, whereas IL-22R1+ intermediate monocytes were negatively correlated with IL-6, IFN-α and CRP in non-severe infections. Moreover, in the absence of in vitro stimulation, NK and CD4+ T cells produced IFN-γ and IL-22, and CD4+ and CD8+ T cells produced IL-17A. CD4+ T lymphocytes also expressed IL-22R1, the density of its expression defining two different functional subsets. In conclusion, we provide the first evidence that SARS-CoV-2 infection is characterized by an abnormal expression of IL22R1 on blood myeloid cells and CD4+ T lymphocytes. Our results suggest that the involvement of the IL-22R1/IL-22 axis could be protective at the beginning of SARS-CoV-2 infection but could shift to a detrimental response over time.

Chemerin plasma levels are increased in COVID-19 patients and are an independent risk factor of mortality

“…As controls, blood samples from health care workers participating to a seroprevalence study (22) in another hospital located in the Brussels Capital Region were used (asymptomatic with negative PCR and serological tests (IgG and IgA)). Within two hours after collection, plasma from EDTA tube was extracted and stored at -20°C and whole blood from another tube was mixed with Cytodelics Stabiliser (Cytodelics AB, Stockholm, Sweden) and stored at -80°C, as previously described (23). Covid and control samples were prepared and stored identically.…”

“…Flow cytometry analysis were performed on an LSR Fortessa instrument (BD Biosciences, Franklin Lakes, NJ, USA) and analyzed using FlowJo software (BD Biosciences, Franklin Lakes, NJ, USA) to identify different immune cell populations and their expression of ChemR23. The gating strategy was previously described by Albayrak et al (23).…”

The role of interleukin-22 in lung health and its therapeutic potential for COVID-19

“…Besides, researchers further demonstrate that IL-22 can reduce the expression of viral entry receptors, such as ACE2, TMPRSS2, and increase the expression of anti-viral proteins through IL-22/IL-22R1 pathway (Figure 4) (95). Thus, these findings suggest that the IL-22/IL-22R1 signaling is involved in the pathological process of COVID-19, which can be protective during SARS-CoV-2 infections (93)(94)(95).…”

“…As the IL-22/IL-22R1 axis is involved in inflammation during virus infection, the expression patterns of IL-22/IL-22R1 on blood hematopoietic cells in SARS-CoV-2 infection have been well studied (90)(91)(92)(93). The numbers of IL-22R1 + myeloid DC1, myeloid DC2, and plasmacytoid DC and the proportions of IL-22R1 + intermediate, non-classical, and classical monocytes higher in COVID-19 patients than controls at the presented day.…”

“…Multivariate analysis is performed on all IL-22R1 + myeloid cells to distinguish the disease severity. However, correlation analysis between the concentration of plasma chemokines and IL-22R1 + cell subsets indicates that some subsets have protective effects, while others have pro-inflammatory effects ( 93 , 94 ). Without stimulation, CD4 + -T and NK lymphocytes produced IL-22.…”