title: Targeting BCL2 family in human myeloid dendritic cells: a challenge to cure diseases with chronic inflammations associated with bone loss.
abstract: 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.
authors.affiliation: Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden.
authors.forename: Selma
authors.initials: S
authors.lastname: Olsson Åkefeldt
authors.forename: Mohamad Bachar
authors.initials: MB
authors.lastname: Ismail
authors.forename: Hélène
authors.initials: H
authors.lastname: Valentin
authors.forename: Maurizio
authors.initials: M
authors.lastname: Aricò
authors.forename: Jan-Inge
authors.initials: JI
authors.lastname: Henter
authors.forename: Christine
authors.initials: C
authors.lastname: Delprat
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001862:Bone Resorption / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D001842:Bone and Bones / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002459:Cell Fusion; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D006646:Histiocytosis, Langerhans-Cell / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D020381:Interleukin-17 / Q000494:pharmacology; D015778:Minor Histocompatibility Antigens; D058990:Molecular Targeted Therapy; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D000893:Anti-Inflammatory Agents; C096816:BCL2-related protein A1; D020381:Interleukin-17; C579095:MCL1 protein, human; D015778:Minor Histocompatibility Antigens; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2