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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 05, 2020 |
| Title |
Expression data from BMDM |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
sex-specific role of p38-MAPK in EAE is regulated by estrogen receptor alpha;
Biological sex is a critical factor in regulating immune function. A striking example of this is the higher prevalence of autoimmune diseases such as multiple sclerosis (MS) and lupus in females compared to males. While many studies have implicated the role of sex hormones such as estrogens and androgens in these sex differences, surprisingly little is known about other molecular pathways that underlie sex differences or interact with sex hormones. We have previously shown that conditional ablation of p38α MAP kinase signaling in myeloid cells (p38αCKO) was protective in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE), in female but not male mice. This sex difference was dependent on the presence of sex hormones, leading us to hypothesize that the pathogenic function of p38α in EAE depends on estrogen signaling via one of the two nuclear estrogen receptors, encoded by Esr1 and Esr2. To test this hypothesis, we performed experiments with p38αCKO macrophages, which demonstrated that the effects of estradiol and p38α were independent of one another in vitro. Since many sex hormone effects are lost in vitro, we generated p38αCKO mice lacking either Esr1 or Esr2, and evaluated their EAE susceptibility in vivo. Myeloid-specific deletion of Esr1 abrogated protection in p38αCKO females, although global deletion of Esr1 and Esr2 did not. Moreover, global or myeloid-specific disruption of Esr1 unexpectedly promoted protection from EAE in p38αCKO males. Mechanistically, Esr1 deletion resulted in partial reprogramming of p38α-dependent transcriptional modules in male macrophages, in particular those regulated by TGFβ, BRD4, and SMARCA4. These results demonstrate that estrogen signaling in myeloid cells plays an important sex-specific role in programming their dependence on specific intracellular signaling pathways in the context of autoimmune disease pathogenesis, suggesting potential avenues for sex-specific therapeutics or combinatorial approaches for the treatment of such diseases.
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| Overall design |
We used microarray to compare the gene expression in three different groups of mice- WT (p38 W and DO W), p38-Conditional knockout (p38 KO) and p38-ESR1-double KO (DO KO)
All our WT and KOs are in C57BL/6 background. P38α and ESR1 were floxed and LysM-cre was used to create the KOs
We collected BMDMs from these three different groups of mice and stimulated them with LPS (100ng/ml) for 4 hours. Then, RNA was extracted and samples were undergone Affymatrix microarray (Clariom S mouse Assays)
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| Contributor(s) |
Sabikunnahar S, McGill M, Krementsov D |
| Citation(s) |
32200131 |
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| Submission date |
Mar 04, 2020 |
| Last update date |
Jun 09, 2022 |
| Contact name |
SABIKUNNAHAR SABIKUNNAHAR |
| E-mail(s) |
ssabikun@uvm.edu
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| Organization name |
The University of Vermont
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| Department |
Biomedical and Health Sciences
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| Lab |
Krementsov Lab
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| Street address |
318 Rowell, 106 Carrigan Dr
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| City |
Burlington |
| State/province |
Vermont |
| ZIP/Postal code |
05405 |
| Country |
USA |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (14)
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| GSM4379108 |
double KO, rep 4 |
| GSM4379109 |
WT, rep 1 |
| GSM4379110 |
WT, rep 2 |
| GSM4379111 |
p38 KO, rep 1 |
| GSM4379112 |
p38 KO, rep 2 |
| GSM4379113 |
p38 KO, rep 3 |
| GSM4379114 |
p38 KO, rep 4 |
| GSM4379115 |
WT, rep 3 |
| GSM4379116 |
WT, rep 4 |
| GSM4379117 |
WT, rep 5 |
| GSM4379118 |
WT, rep 6 |
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| Relations |
| BioProject |
PRJNA610258 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE146370_RAW.tar |
15.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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