Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis

Acute cellular rejection (ACR) remains as one of the main causes of graft loss and death in intestinal transplant (ITx) patients. ACR promotes intestinal injury, disruption of the mucosal barrier, bacterial translocation, and organ dysfunction. As epithelial regeneration is critical in reversing the...

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Autores principales: Pucci Molineris, Melisa Eliana, González Polo, Virginia, Rumbo, Carolina, Fuxman, Claudia, Lowestein, Carlos, Nachman, Fabio, Rumbo, Martín, Gondolesi, Gabriel Eduardo, Meier, Dominik
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Ciencias Médicas
Intestinal transplant
Acute rejection
Innate lymphoid cells
Interleukin-22
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/162669
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-162669
record_format dspace
spelling I19-R120-10915-1626692024-02-15T04:07:05Z http://sedici.unlp.edu.ar/handle/10915/162669 Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis Pucci Molineris, Melisa Eliana González Polo, Virginia Rumbo, Carolina Fuxman, Claudia Lowestein, Carlos Nachman, Fabio Rumbo, Martín Gondolesi, Gabriel Eduardo Meier, Dominik 2020-06-01 2024-02-14T18:44:39Z en Ciencias Médicas Intestinal transplant Acute rejection Innate lymphoid cells Interleukin-22 Acute cellular rejection (ACR) remains as one of the main causes of graft loss and death in intestinal transplant (ITx) patients. ACR promotes intestinal injury, disruption of the mucosal barrier, bacterial translocation, and organ dysfunction. As epithelial regeneration is critical in reversing these consequences, the functional axis between the innate lymphoid cell subpopulation 3 (ILC3) and interleukin 22 plays an essential role in that process. Natural-cytotoxic-receptor–positive (NCR+) ILC3 cells have been demonstrated to induce intestinal-stem-cell proliferation along with an IL-22–dependent expansion of that population in several intestinal pathologies, though thus far not after ITx. Therefore, we intended to determine the impact of chronic immunosuppression and ACR on ILC3 cells and interleukin-22 (IL-22) production in the lamina propria after that intervention. Materials and methods We compared biopsies from healthy volunteers with biopsies from ITx recipients without or with mild-to-moderate ACR, using flow cytometry and the quantitative-PCR. Results NCR+ ILC3 cells were found to be unaffected by immunosuppression at different time points posttransplant when patients did not experience ACR, but were diminished upon the occurrence of ACR independently of the post-ITx time. Moreover, IL-22–expression levels were notably reduced in ACR. Conclusion The NCR+-ILC3/IL-22 axis is impaired during ACR contributing to a delay in or lack of a complete and efficient epithelial regeneration. Thus, our findings reveal that IL-22 analogues could potentially be used as a new complementary therapeutic approach, in conjunction with immunosuppressant drugs, in order to promote mucosal regeneration upon ACR. Consejo Nacional de Investigaciones Científicas y Técnicas Instituto de Estudios Inmunológicos y Fisiopatológicos Articulo Articulo http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Intestinal transplant
Acute rejection
Innate lymphoid cells
Interleukin-22
spellingShingle Ciencias Médicas
Intestinal transplant
Acute rejection
Innate lymphoid cells
Interleukin-22
Pucci Molineris, Melisa Eliana
González Polo, Virginia
Rumbo, Carolina
Fuxman, Claudia
Lowestein, Carlos
Nachman, Fabio
Rumbo, Martín
Gondolesi, Gabriel Eduardo
Meier, Dominik
Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis
topic_facet Ciencias Médicas
Intestinal transplant
Acute rejection
Innate lymphoid cells
Interleukin-22
description Acute cellular rejection (ACR) remains as one of the main causes of graft loss and death in intestinal transplant (ITx) patients. ACR promotes intestinal injury, disruption of the mucosal barrier, bacterial translocation, and organ dysfunction. As epithelial regeneration is critical in reversing these consequences, the functional axis between the innate lymphoid cell subpopulation 3 (ILC3) and interleukin 22 plays an essential role in that process. Natural-cytotoxic-receptor–positive (NCR+) ILC3 cells have been demonstrated to induce intestinal-stem-cell proliferation along with an IL-22–dependent expansion of that population in several intestinal pathologies, though thus far not after ITx. Therefore, we intended to determine the impact of chronic immunosuppression and ACR on ILC3 cells and interleukin-22 (IL-22) production in the lamina propria after that intervention. Materials and methods We compared biopsies from healthy volunteers with biopsies from ITx recipients without or with mild-to-moderate ACR, using flow cytometry and the quantitative-PCR. Results NCR+ ILC3 cells were found to be unaffected by immunosuppression at different time points posttransplant when patients did not experience ACR, but were diminished upon the occurrence of ACR independently of the post-ITx time. Moreover, IL-22–expression levels were notably reduced in ACR. Conclusion The NCR+-ILC3/IL-22 axis is impaired during ACR contributing to a delay in or lack of a complete and efficient epithelial regeneration. Thus, our findings reveal that IL-22 analogues could potentially be used as a new complementary therapeutic approach, in conjunction with immunosuppressant drugs, in order to promote mucosal regeneration upon ACR.
format Articulo
Articulo
author Pucci Molineris, Melisa Eliana
González Polo, Virginia
Rumbo, Carolina
Fuxman, Claudia
Lowestein, Carlos
Nachman, Fabio
Rumbo, Martín
Gondolesi, Gabriel Eduardo
Meier, Dominik
author_facet Pucci Molineris, Melisa Eliana
González Polo, Virginia
Rumbo, Carolina
Fuxman, Claudia
Lowestein, Carlos
Nachman, Fabio
Rumbo, Martín
Gondolesi, Gabriel Eduardo
Meier, Dominik
author_sort Pucci Molineris, Melisa Eliana
title Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis
title_short Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis
title_full Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis
title_fullStr Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis
title_full_unstemmed Acute cellular rejection in small-bowel transplantation impairs NCR+ innate lymphoid cell subpopulation 3/interleukin 22 axis
title_sort acute cellular rejection in small-bowel transplantation impairs ncr+ innate lymphoid cell subpopulation 3/interleukin 22 axis
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/162669
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