IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View.

In this historical perspective, written in honor of Dr. William E. Paul, we describe the initial discovery of one of the dominant substrates for tyrosine phosphorylation stimulated by IL-4. We further describe how this "IL-4-induced phosphorylated substrate" (4PS) was characterized as a member of the insulin receptor substrate (IRS) family of large adaptor proteins that link IL-4 and insulin receptors to activation of the phosphatidyl-inositol 3' kinase pathway as well as other downstream signaling pathways. The relative contribution of the 4PS/IRS pathway to the early models of IL-4-induced proliferation and suppression of apoptosis are compared to our more recent understanding of the complex interplay between positive and negative regulatory pathways emanating from members of the IRS family that impact allergic responses.

Expression of interleukin-13 and its receptors in mycosis fungoides / 中华皮肤科杂志

Objective To measure the expression of interleukin-13 (IL-13) and its receptors in mycosis fungoides (MF) lesions,and to investigate their clinical significance.Methods A total of 34 paraffin-embedded specimens of MF,which was confirmed by clinical and histopathological features,immunophenotyping and/or T-cell receptor gene rearrangements,were collected from Hangzhou Third People's Hospital between January 2010 and March 2016.According to the tumor-node-metastasis (TNM) staging system,5 patients were at stage I A,9 at stage Ⅰ B,17 at stage Ⅱ A,and 3 at stage Ⅱ B.Ten normal skin tissue specimens served as controls.Immunohistochemical study was conducted to measure the expression of IL-13,IL-13Rα1 and IL-13Rα2.Results IL-13,IL-13Rα1 and IL-13Rα2 were all expressed in atypical lymphoid cells and epidermotropic lymphoid cells in MF lesions at various stages.IL-13Rα2 was highly expressed in all the MF lesions.None of IL-13 and its receptors were expressed in normal skin tissues and lymphocytes.The expression rates of IL-13 and its receptors in MF lesions increased along with the progression of MF.Additionally,the expression rates of IL-13 (10.00％ ± 3.14％),IL-13Rα1 (21.43％ ± 6.88％) and IL-13Ro2 (31.14％ ± 6.38％) significantly decreased in MF lesions at stage Ⅰ compared with those at stage Ⅱ (27.50％ ± 11.00％,39.45％ ± 9.43％,44.40％ ± 11.15％,respectively,all P ＜ 0.05),but no significant differences were observed between stage Ⅰ A and Ⅰ B,or between stage Ⅱ A and Ⅱ B (P ＞ 0.05).Conclusion IL-13 and its receptors,especially IL-13Rα2,may be expected to serve as biomarkers for early diagnosis of MF and prediction of its biological behaviors.

Interleukin-13 and its receptors in idiopathic interstitial pneumonia: clinical implications for lung function.

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-gamma has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-gamma were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Ralpha1/alpha2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-gamma levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Ralpha1, rather than IL-13Ralpha2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.

Interleukin-13 and Its Receptors in Idiopathic Interstitial Pneumonia: Clinical Implications for Lung Function

Idiopathic interstitial pneumonia (IIP) is characterized by varying degrees of interstitial fibrosis. IL-13 and IL-4 are strong inducers of tissue fibrosis, whereas IFN-gamma has antifibrotic potential. However, the roles of these substances in IIP remain unknown. IL-13, IL-4, and IFN-gamma were measured in the BAL fluid of 16 idiopathic pulmonary fibrosis (IPF) patients, 10 nonspecific interstitial pneumonia (NSIP) patients, and 8 normal controls. The expression of IL-13 and IL-13Ralpha1/alpha2 in lung tissues was analyzed using ELISA and immunohistochemistry. IL-13 levels were significantly higher in IPF patients than the others (P<0.05). IL-4 levels were higher in both IPF and NSIP patients than in normal controls (P<0.05), and IFN-gamma levels were lower in NSIP patients than in normal controls (P=0.047). IL-13 levels correlated inversely with FVC% (r=-0.47, P=0.043) and DLCO% (r=-0.58, P=0.014) in IPF and NSIP patients. IL-13 was strongly expressed in the smooth muscle, bronchial epithelium, alveolar macrophages and endothelium of IPF patients. IL-13Ralpha1, rather than IL-13Ralpha2, was strongly expressed in the smooth muscle, bronchial epithelium, and endothelium of IPF patients. IL-13 and its receptors may contribute to the pathogenesis of fibrosis in IIP and appear to be related to the severity of the disease.