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Query: UMLS:C0019621 (
Langerhans cell histiocytosis
)
3,250
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
.
...
PMID:Targeting BCL2 family in human myeloid dendritic cells: a challenge to cure diseases with chronic inflammations associated with bone loss. 2376 95
Langerhans cell histiocytosis
(
LCH
) is an inflammatory myeloid neoplasia characterized by granulomatous lesions containing pathological CD207
+
dendritic cells (DCs) with constitutively activated mitogen-activated protein kinase (MAPK) pathway signaling. Approximately 60% of
LCH
patients harbor somatic
BRAF
V600E mutations localizing to CD207
+
DCs within lesions. However, the mechanisms driving
BRAF
V600E
+
LCH
cell accumulation in lesions remain unknown. Here we show that sustained extracellular signal-related kinase activity induced by
BRAF
V600E inhibits C-C motif chemokine receptor 7 (CCR7)-mediated DC migration, trapping DCs in tissue lesions. Additionally,
BRAF
V600E increases expression of
BCL2
-like protein 1 (BCL2L1) in DCs, resulting in resistance to apoptosis. Pharmacological MAPK inhibition restores migration and apoptosis potential in a mouse
LCH
model, as well as in primary human
LCH
cells. We also demonstrate that MEK inhibitor-loaded nanoparticles have the capacity to concentrate drug delivery to phagocytic cells, significantly reducing off-target toxicity. Collectively, our results indicate that MAPK tightly suppresses DC migration and augments DC survival, rendering DCs in
LCH
lesions trapped and resistant to cell death.
...
PMID:RAF/MEK/extracellular signal-related kinase pathway suppresses dendritic cell migration and traps dendritic cells in Langerhans cell histiocytosis lesions. 2926 18
