Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss

Rheumatoid arthritis (RA) and Langerhans cell histiocytosis (LCH) are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC), and, especially, regulating the...

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Main Authors: Selma Olsson Åkefeldt, Mohamad Bachar Ismail, Hélène Valentin, Maurizio Aricò, Jan-Inge Henter, Christine Delprat
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2013/701305
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author Selma Olsson Åkefeldt
Mohamad Bachar Ismail
Hélène Valentin
Maurizio Aricò
Jan-Inge Henter
Christine Delprat
author_facet Selma Olsson Åkefeldt
Mohamad Bachar Ismail
Hélène Valentin
Maurizio Aricò
Jan-Inge Henter
Christine Delprat
author_sort Selma Olsson Åkefeldt
collection DOAJ
description Rheumatoid arthritis (RA) and Langerhans cell histiocytosis (LCH) are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC), and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.
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spelling doaj-art-39e805a5c19e4bcc97a75dea9351a3922025-08-20T02:24:13ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/701305701305Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone LossSelma Olsson Åkefeldt0Mohamad Bachar Ismail1Hélène Valentin2Maurizio Aricò3Jan-Inge Henter4Christine Delprat5Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, SwedenCNRS, UMR5239, Laboratoire de Biologie Moléculaire de la Cellule, 69007 Lyon, FranceCNRS, UMR5239, Laboratoire de Biologie Moléculaire de la Cellule, 69007 Lyon, FranceDepartment of Pediatric Hematology Oncology, Azienda Ospedaliero-Universitaria, Meyer Children's Hospital, 50139 Florence, ItalyChildhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, SwedenCNRS, UMR5239, Laboratoire de Biologie Moléculaire de la Cellule, 69007 Lyon, FranceRheumatoid arthritis (RA) and Langerhans cell histiocytosis (LCH) are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC), and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.http://dx.doi.org/10.1155/2013/701305
spellingShingle Selma Olsson Åkefeldt
Mohamad Bachar Ismail
Hélène Valentin
Maurizio Aricò
Jan-Inge Henter
Christine Delprat
Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss
Clinical and Developmental Immunology
title Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss
title_full Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss
title_fullStr Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss
title_full_unstemmed Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss
title_short Targeting BCL2 Family in Human Myeloid Dendritic Cells: A Challenge to Cure Diseases with Chronic Inflammations Associated with Bone Loss
title_sort targeting bcl2 family in human myeloid dendritic cells a challenge to cure diseases with chronic inflammations associated with bone loss
url http://dx.doi.org/10.1155/2013/701305
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