Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice

Systemic lupus erythematosus is characterized by high levels of IgG class autoantibodies that contribute to the pathophysiology of the disease. The formation of these autoantibodies occurs in the germinal centers, where there is cooperation between follicular T helper cells (TFH) and autoreactive B...

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Main Authors: Yolanda P. Alemán-García, Ricardo M. Vaquero-García, Rocio Flores-Fernández, Ezequiel M. Fuentes-Pananá, Patricia Gorocica-Rosete, Alberto Pizaña-Venegas, Luis Chávez-Sanchéz, Francico Blanco-Favela, María V. Legorreta-Haquet, Adriana K. Chávez-Rueda
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2021/6630715
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author Yolanda P. Alemán-García
Ricardo M. Vaquero-García
Rocio Flores-Fernández
Ezequiel M. Fuentes-Pananá
Patricia Gorocica-Rosete
Alberto Pizaña-Venegas
Luis Chávez-Sanchéz
Francico Blanco-Favela
María V. Legorreta-Haquet
Adriana K. Chávez-Rueda
author_facet Yolanda P. Alemán-García
Ricardo M. Vaquero-García
Rocio Flores-Fernández
Ezequiel M. Fuentes-Pananá
Patricia Gorocica-Rosete
Alberto Pizaña-Venegas
Luis Chávez-Sanchéz
Francico Blanco-Favela
María V. Legorreta-Haquet
Adriana K. Chávez-Rueda
author_sort Yolanda P. Alemán-García
collection DOAJ
description Systemic lupus erythematosus is characterized by high levels of IgG class autoantibodies that contribute to the pathophysiology of the disease. The formation of these autoantibodies occurs in the germinal centers, where there is cooperation between follicular T helper cells (TFH) and autoreactive B cells. Prolactin has been reported to exacerbate the clinical manifestations of lupus by increasing autoantibody concentrations. The objective of this study was to characterize the participation of prolactin in the differentiation and activation of TFH cells, by performing in vivo and in vitro tests with lupus-prone mice, using flow cytometry and real-time PCR. We found that TFH cells express the long isoform of the prolactin receptor and promoted STAT3 phosphorylation. Receptor expression was higher in MRL/lpr mice and correlative with the manifestations of the disease. Although prolactin does not intervene in the differentiation of TFH cells, it does favor their activation by increasing the percentage of TFH OX40+ and TFH IL21+ cells, as well as leading to high serum concentrations of IL21. These results support a mechanism in which prolactin participates in the emergence of lupus by inducing overactive TFH cells and perhaps promoting dysfunctional germinal centers.
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spelling doaj-art-a4e3d9ead16749f0a49ecd28b8c07fa72025-08-20T02:23:05ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/66307156630715Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr MiceYolanda P. Alemán-García0Ricardo M. Vaquero-García1Rocio Flores-Fernández2Ezequiel M. Fuentes-Pananá3Patricia Gorocica-Rosete4Alberto Pizaña-Venegas5Luis Chávez-Sanchéz6Francico Blanco-Favela7María V. Legorreta-Haquet8Adriana K. Chávez-Rueda9UIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social, MexicoUIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social, MexicoUIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social, MexicoUnidad de Investigación en Virología y Cáncer, Hospital Infantil de México “Federico Gómez”, MexicoDepartamento de Investigación en Bioquímica, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosió Villegas”, MexicoUnidad de Investigación y Bioterio, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosió Villegas”, MexicoUIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social, MexicoUIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social, MexicoUIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social, MexicoUIM en Inmunología, Hospital de Pediatría, CMN Siglo XXI, Instituto Mexicano del Seguro Social, MexicoSystemic lupus erythematosus is characterized by high levels of IgG class autoantibodies that contribute to the pathophysiology of the disease. The formation of these autoantibodies occurs in the germinal centers, where there is cooperation between follicular T helper cells (TFH) and autoreactive B cells. Prolactin has been reported to exacerbate the clinical manifestations of lupus by increasing autoantibody concentrations. The objective of this study was to characterize the participation of prolactin in the differentiation and activation of TFH cells, by performing in vivo and in vitro tests with lupus-prone mice, using flow cytometry and real-time PCR. We found that TFH cells express the long isoform of the prolactin receptor and promoted STAT3 phosphorylation. Receptor expression was higher in MRL/lpr mice and correlative with the manifestations of the disease. Although prolactin does not intervene in the differentiation of TFH cells, it does favor their activation by increasing the percentage of TFH OX40+ and TFH IL21+ cells, as well as leading to high serum concentrations of IL21. These results support a mechanism in which prolactin participates in the emergence of lupus by inducing overactive TFH cells and perhaps promoting dysfunctional germinal centers.http://dx.doi.org/10.1155/2021/6630715
spellingShingle Yolanda P. Alemán-García
Ricardo M. Vaquero-García
Rocio Flores-Fernández
Ezequiel M. Fuentes-Pananá
Patricia Gorocica-Rosete
Alberto Pizaña-Venegas
Luis Chávez-Sanchéz
Francico Blanco-Favela
María V. Legorreta-Haquet
Adriana K. Chávez-Rueda
Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice
Journal of Immunology Research
title Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice
title_full Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice
title_fullStr Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice
title_full_unstemmed Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice
title_short Prolactin Increases the Frequency of Follicular T Helper Cells with Enhanced IL21 Secretion and OX40 Expression in Lupus-Prone MRL/lpr Mice
title_sort prolactin increases the frequency of follicular t helper cells with enhanced il21 secretion and ox40 expression in lupus prone mrl lpr mice
url http://dx.doi.org/10.1155/2021/6630715
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