Redistribution of TNF Receptor 1 and 2 Expression on Immune Cells in Patients with Bronchial Asthma

Abstract

Background: The co-expression patterns of type 1 and 2 tumor necrosis factor (TNF)-α membrane receptors (TNFR1/TNFR2) are associated with the presence, stage, and activity of allergic diseases. The aim of this study was to assess the expression levels and dynamics of TNFRs on immune cells and to assess associations between their expression and severity of bronchial asthma (BA). Methods: Patients with severe (n = 8), moderate (n = 10), and mild (n = 4) BA were enrolled. As a comparison group, data from 46 healthy volunteers (HV) were accessed. Co-expression of TNFR1/2 was evaluated as a percentage of cells and the number of receptors of each type per cell. Multivariate logistic regression analysis was used to identify diagnostic biomarkers of BA. Results: More than 90% of the monocytes in patients with mild BA were TNFR1+TNFR2+ but had significantly lower TNFR1 expression density compared with HV (7.82- to 14.08-fold, depending on disease severity). Lower percentages of the TNFR+ B-lymphocytes were observed in combination with significantly lower receptors density in BA compared with HV (2.59- to 11.64-fold for TNFR1 and 1.72- to 3.4-fold for TNFR2, depending on disease severity). The final multivariate model for predicting the presence of BA included the percentage of double-positive CD5+ B-lymphocytes and average number of TNFR1 molecules expressed on cytotoxic naive T-lymphocytes and T-helper cells (R2 = 0.87). Conclusions: The co-expression patterns of TNFRs on immune cells in BA differed significantly compared with HV. The expression differences were associated with disease severity. TNFR1 expression changes were key parameters that discriminated patients with BA from those with HV.

Sequential treatment with a TNFR2 agonist and a TNFR1 antagonist improves outcomes in a humanized mouse model for MS

“…There are two molecular variants of TNF, namely a transmembrane-bound TNF (tmTNF) and a soluble TNF (sTNF), displaying different affinities for the two receptors: tmTNF is the preferable ligand of TNFR2 [ 8 ] and sTNF exhibits higher affinity for TNFR1 [ 9 ]. TNFRs are involved in many physiological functions [ 1 , 10 – 12 ] and are differentially expressed on the surface of many different cell types such as immune [ 13 – 15 ] and central nervous system (CNS) cells [ 16 – 18 ]. Furthermore, the two receptors differ in the intracellular signaling pathways they trigger, thereby leading to different cellular responses.…”

TNFα Causes a Shift in Gene Expression of TNFRSF1A and TNFRSF1B Isoforms

“…By interacting with its receptors TNFR1 and TNFR2, the tumor necrosis factor α (TNFα) ligand is involved in the inflammatory response activation, cell proliferation, and differentiation [4]. TNF-α receptor expression levels have been shown to change significantly in immunopathological conditions of various etiologies, such as bronchial asthma [5] and rheumatoid arthritis [6], with the severity and duration of the disease also affecting the distribution of receptor expression on immunocompetent cells [7].…”