INVESTIGADORES
CURCIARELLO Renata
congresos y reuniones científicas
Título:
IL-13 promoted the phosphorylation of STAT3 and STAT6 on colonic epithelial cells with the secretion of TSLP and CCL26
Autor/es:
JULIÁN VACCARO; KARINA EVA CANZIANI; LUCIANA GUZMÁN; VIVIANA BERNEDO; MARCELA GARCÍA; EUGENIA M ALTAMIRANO; RENATA CURCIARELLO; CECILIA ISABEL MUGLIA; GUILLERMO HORACIO DOCENA
Reunión:
Congreso; Reunión Conjunta SAIC SAI AAFE NanoMed; 2021
Resumen:
Food allergy is rapidly increasing in prevalenceprevalence isincreasing worldwide and is one of the main triggers of anaphylaxis.Eosinophilic inflammatory responses can be associated with food allergy and theunderlying mechanisms in human colonic mucosa are poorly understood. Wepreviously reported that allergic sensitized pediatric patients with juvenilepolyps showed local IgE class-switch recombination with high levels of TSLP,IL-33 and CCL26 (the main chemoattractant for eosinophils), that might berelated with the hypereosinophilia. This study aimed to investigate theintestinal epithelial cells as a source for these soluble mediators underdifferent inflammatory settings.Caco-2 cells were stimulated with IL-13 (10 ng/ml) orIFN-γ(10 ng/ml) and CCL26, TSLP and IL-33 were evaluated by ELISA in culturesupernatants. Cell activation was analyzed with a tyrosine-kinasephosphorylation array and finally, kinase activation was confirmed byimmunoblotting. Comparisonbetween groups was made using Student´s t-test. Results were expressed as mean ±standard error of the mean. Differences between means were consideredstatistically significant when (p<0.1).[R1] We found that TSLP and CCL26 levels were significantlyincreased in Caco-2 cells in response to IL-13 (p<0.1 in 3independent experiments), whereas it remained unchangedfollowing the stimulation with IFN-γ. Cell activation wasalso demonstrated by analyzing the tyrosine-kinase activation, and we foundthat STAT-3, STAT-6, Lck, Akt, IGF-IR were higher phosphorylated upon IL-13stimulus than cells exposed to IFN-γor medium(p<0,1). No effect wasobserved on IL-33 secretion under the conditionsstudied.In conclusion, our findings show that colonicepithelial cells respond to a Th2 environment by secreting TSLP, which maypromote mucosal type-2 inflammation through ILC2 activation, and CCL26, whichis probably involved in the eosinophil chemoattraction. The IL-13-driven cellactivation involves the STAT3, STAT6 pathways, and other kinases. Thesefindings may pave the way to identify the mucosal epithelial cells as thetriggers of inflammation and eosinophil-rich cell infiltration, and thetyrosine phosphorylation as a therapeutic target. [R1]Yo no pondríaesto acá, sí en el poster. Porque no estás poniendo los valores numéricos deesos resultados en el párrafo sguiente. Sino tenés que poner  los valores de TSLP y CCL26 que te dio conIL-13 vs IFN o basal...