 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on May 24, 2023 |
| Title |
RANK+TLR2+ Myeloid Subpopulation Converts Autoimmune to Joint Destruction in Rheumatoid Arthritis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Joint destruction is the major clinic burden in patients with rheumatoid arthritis (RA). It is unclear, though, how this autoimmune disease progresses to the point of deterioration of the joint. Here, we report that in a mouse model of RA the upregulation of TLR2 expression and its a(2,3) sialylation in RANK+ myeloid monocytes mediate the transition from autoimmunity to osteoclast fusion and bone resorption, resulting in joint destruction. The expression of a(2,3) sialyltransferases were significantly increased in RANK+TLR2+ myeloid monocytes, and their inhibition or treatment with a TLR2 inhibitor blocked osteoclast fusion. Notably, analysis of our single-cell RNA-sequencing (scRNA-seq) libraries generated from RA mice revealed a novel RANK+TLR2- subset that negatively regulated osteoclast fusion. Importantly, the RANK+TLR2+ subset was significantly diminished with the treatments. Moreover, the RANK+TLR2- subset could differentiate into a TRAP+ osteoclast lineage, but the resulting cells did not fuse to form osteoclasts. Our scRNA-seq data showed that Maf is highly expressed in the RANK+TLR2- subset, and the a(2,3) sialyltransferase inhibitor induced Maf expression in the RANK+TLR2+ subset. The identification of a RANK+TLR2- subset provides a potential explanation for TRAP+ mononuclear cells in bone and their anabolic activity. Further, TLR2 expression and its a(2,3) sialylation in the RANK+ myeloid monocytes could be effective targets to prevent autoimmune-mediated joint destruction.
|
| |
|
| Overall design |
Intestinal GCs of the RedMUC298trTg mice were isolated by Fluorescence-activated cell sorting (FACS) according to the presence or absence of mCherry signal and analyzed using scRNAseq.
|
| Web link |
https://elifesciences.org/articles/85553
|
| |
|
| Contributor(s) |
Weixin Z, Kathleen N, Gehua Z, Janet C, Mei W, Patrick C, Xu C |
| Citation(s) |
37204303 |
| |
| Submission date |
Dec 23, 2022 |
| Last update date |
May 27, 2023 |
| Contact name |
Kathleen Noller |
| E-mail(s) |
katkats1@jhmi.edu
|
| Organization name |
Johns Hopkins University
|
| Street address |
3400 N. Charles Street
|
| City |
Baltimore |
| State/province |
MD |
| ZIP/Postal code |
21218 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (3) |
| GSM6893371 |
Collagen-induced arthritis (CIA), scRNA-seq |
| GSM6893372 |
CIA + soyasaponin Bb treatment (CIA treated), scRNA-seq |
| GSM6893373 |
DBA control, scRNA-seq |
|
| Relations |
| BioProject |
PRJNA915396 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE221704_RAW.tar |
184.8 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
