Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P06126 (
CD1a
)
2,221
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Immune thrombocytopenia
(
ITP
) is an autoimmune disease in which dendritic cells (DCs) play a crucial role in the breakdown of self-tolerance. Studies have identified the function of mesenchymal stem cells (MSCs) in promoting the development of regulatory DCs (regDCs). Our previous work revealed that MSCs in
ITP
exerted senescence, apoptosis, and impaired immunosuppressive effects on T and B cells. However, it is unclear whether the effects of MSCs on regDC induction are altered in
ITP
. Our data demonstrated that MSCs in
ITP
were impaired in inhibiting
CD1a
+
DC and CD14
+
DC differentiation from CD34
+
hematopoietic progenitor cells (CD34
+
HPCs). DCs differentiated with MSCs in
ITP
exhibited an increased expression of costimulatory molecules CD80/CD86 and secretion of proinflammatory interleukin-12 (IL-12). Accordingly, the tolerogenic characteristics were deficient in DCs induced by MSCs in
ITP
. DCs differentiated with MSCs in
ITP
exhibited an impaired ability to inhibit CD3
+
T cell proliferation, to suppress T helper (Th)1 cell differentiation, and to induce anergic and regulatory T cells (Tregs). The expression of Notch signaling components was measured in MSCs in
ITP
. Reduced expression of the ligand Jagged-1, the receptor Notch-1 intracellular domain (NICD-1), and the target gene Hes-1 was identified in MSCs in
ITP
. The addition of biologically active Jagged-1 to CD34
+
HPCs was observed to promote regDC differentiation. When cultured on Jagged-1-coated plates, MSCs in
ITP
showed an enhancement of the Notch-1 pathway activation, Jagged-1 expression, and the function in inducing regDCs. Pretreatment with all-trans retinoic acid (ATRA) was found to partially restore the capacity of MSCs in both
ITP
patients and healthy controls in inducing CD34
+
-derived regDCs. Our data elucidated that MSCs in
ITP
were impaired in inducing CD34
+
-regDCs, associated with the Notch-1/Jagged-1 signaling pathway. ATRA could partially correct the impairment of MSCs, suggesting that ATRA could serve as a potential therapeutic alternative for
ITP
.
...
PMID:Impaired Function of Bone Marrow Mesenchymal Stem Cells from Immune Thrombocytopenia Patients in Inducing Regulatory Dendritic Cell Differentiation Through the Notch-1/Jagged-1 Signaling Pathway. 2894 11
