Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling

We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface....

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Main Authors: Karla F. Corral-Jara, Jorge L. Trujillo-Ochoa, Mauricio Realpe, Arturo Panduro, Juan F. Gómez-Leyva, Yvonne Rosenstein, Alexis Jose-Abrego, Sonia Roman, Nora A. Fierro
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2016/1759027
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author Karla F. Corral-Jara
Jorge L. Trujillo-Ochoa
Mauricio Realpe
Arturo Panduro
Juan F. Gómez-Leyva
Yvonne Rosenstein
Alexis Jose-Abrego
Sonia Roman
Nora A. Fierro
author_facet Karla F. Corral-Jara
Jorge L. Trujillo-Ochoa
Mauricio Realpe
Arturo Panduro
Juan F. Gómez-Leyva
Yvonne Rosenstein
Alexis Jose-Abrego
Sonia Roman
Nora A. Fierro
author_sort Karla F. Corral-Jara
collection DOAJ
description We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein, in vitro stimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor gene HAVCR1/TIM-1 was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1.
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spelling doaj-art-ad59a13da8ff401c9bd91602dc2104ca2025-08-20T02:20:34ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/17590271759027Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular SignalingKarla F. Corral-Jara0Jorge L. Trujillo-Ochoa1Mauricio Realpe2Arturo Panduro3Juan F. Gómez-Leyva4Yvonne Rosenstein5Alexis Jose-Abrego6Sonia Roman7Nora A. Fierro8Unidad de Inmunovirología, Servicio de Biología Molecular en Medicina, Hospital Civil de Guadalajara “Fray Antonio Alcalde”, 44280 Guadalajara, JAL, MexicoUnidad de Inmunovirología, Servicio de Biología Molecular en Medicina, Hospital Civil de Guadalajara “Fray Antonio Alcalde”, 44280 Guadalajara, JAL, MexicoDepartamento de Medicina Veterinaria, Centro Universitario de Ciencias Biológicas y Agropecuarias, Universidad de Guadalajara, 44100 Guadalajara, JAL, MexicoServicio de Biología Molecular en Medicina, Hospital Civil of Guadalajara “Fray Antonio Alcalde”, 44280 Guadalajara, JAL, MexicoInstituto Tecnológico de Tlajomulco, 45640 Tlajomulco, JAL, MexicoDepartamento de Medicina Molecular y Bioprocesos, Instituto de Biotecnología, Universidad Nacional Autónoma de México, 62210 Ciudad de México, MexicoDepartamento de Biología Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44100 Guadalajara, JAL, MexicoDepartamento de Biología Molecular, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, 44100 Guadalajara, JAL, MexicoUnidad de Inmunovirología, Servicio de Biología Molecular en Medicina, Hospital Civil de Guadalajara “Fray Antonio Alcalde”, 44280 Guadalajara, JAL, MexicoWe recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein, in vitro stimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor gene HAVCR1/TIM-1 was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1.http://dx.doi.org/10.1155/2016/1759027
spellingShingle Karla F. Corral-Jara
Jorge L. Trujillo-Ochoa
Mauricio Realpe
Arturo Panduro
Juan F. Gómez-Leyva
Yvonne Rosenstein
Alexis Jose-Abrego
Sonia Roman
Nora A. Fierro
Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling
Mediators of Inflammation
title Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling
title_full Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling
title_fullStr Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling
title_full_unstemmed Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling
title_short Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling
title_sort conjugated bilirubin differentially regulates cd4 t effector cells and t regulatory cell function through outside in and inside out mechanisms the effects of hav cell surface receptor and intracellular signaling
url http://dx.doi.org/10.1155/2016/1759027
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