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

被引:9
作者
Akefeldt, Selma Olsson [1 ,2 ,3 ,4 ,5 ]
Ismail, Mohamad Bachar [2 ,3 ,4 ,5 ]
Valentin, Helene [2 ,3 ,4 ,5 ]
Arico, Maurizio [6 ]
Henter, Jan-Inge [1 ]
Delprat, Christine [2 ,3 ,4 ,5 ,7 ,8 ]
机构
[1] Karolinska Univ Hosp Solna, Karolinska Inst, Dept Womens & Childrens Hlth, Childhood Canc Res Unit, S-17176 Stockholm, Sweden
[2] CNRS, Lab Biol Mol Cellule, UMR5239, F-69007 Lyon, France
[3] Ecole Normale Super Lyon, F-69007 Lyon, France
[4] Univ Lyon, F-69003 Lyon, France
[5] Univ Lyon 1, F-69622 Villeurbanne, France
[6] Meyer Childrens Hosp, Azienda Osped Univ, Dept Pediat Hematol Oncol, I-50139 Florence, Italy
[7] Inst Univ France, F-75005 Paris, France
[8] Fac Med Lyon Sud, CNRS 5239, F-69921 Oullins, France
来源
CLINICAL & DEVELOPMENTAL IMMUNOLOGY | 2013年
基金
瑞典研究理事会;
关键词
RHEUMATOID-ARTHRITIS; GENE-EXPRESSION; T-CELLS; APOPTOSIS; HISTIOCYTOSIS; MCL-1; ACTIVATION; RESISTANCE; PROTEINS; INDUCTION;
D O I
10.1155/2013/701305
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页数:11
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