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Ligation of TLR Homologue CD180 of B Cells Activates the PI3K/Akt/mTOR Pathway in Systemic Sclerosis and Induces a Pathological Shift in the Expression of BAFF Receptors
- Source :
- International Journal of Molecular Sciences; Volume 23; Issue 12; Pages: 6777
- Publication Year :
- 2022
-
Abstract
- The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) pathways are known to play a key role in B-cell activation and fibrosis in systemic sclerosis (SSc). Receptors of B-cell activator factor (BAFF) utilize these pathways, which can be influenced by Toll-like receptors (TLRs), as TLRs can alter the expression of BAFF-binding receptors. Our results show that B-cell stimulation via TLR homologue CD180 phosphorylates Akt in diffuse cutaneous SSc (dcSSc) to a lower extent than in healthy controls (HCs). We found basal downregulated BAFF receptor (BAFF-R) and enhanced transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) expression in dcSSc B cells, which might enhance the formation of autoantibody-secreting plasma cells. Moreover, this pathological shift was observed in naive B cells, emphasizing the importance of their increase in SSc. Additionally, we measured higher serum levels of autoantibodies to BAFF in dcSSc patients, suggesting that an imbalance in the complex system of BAFF/anti-BAFF autoantibodies/BAFF-binding receptors may contribute to the development of SSc. Anti-CD180 antibody treatment had opposite effects on the expression of BAFF-R and TACI in HC B cells, resulting in similar levels as observed in SSc B cells without stimulation, which argues against the usefulness of such therapy in SSc.
- Subjects :
- B-Lymphocytes
Scleroderma, Systemic
TOR Serine-Threonine Kinases
Organic Chemistry
Toll-Like Receptors
General Medicine
Catalysis
Computer Science Applications
Inorganic Chemistry
stomatognathic diseases
Phosphatidylinositol 3-Kinases
Antigens, CD
B-Cell Activating Factor
Humans
Physical and Theoretical Chemistry
Phosphatidylinositol 3-Kinase
skin and connective tissue diseases
CD180
TLR
B cells
PI3K/Akt
mTOR
BAFF-R
TACI
anti-BAFF autoantibody
systemic sclerosis
Molecular Biology
Proto-Oncogene Proteins c-akt
Spectroscopy
Autoantibodies
B-Cell Activation Factor Receptor
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 23
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- International journal of molecular sciences
- Accession number :
- edsair.doi.dedup.....5d96a0bb1f70e85a48f39231718dbd2a