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SOCS2 expression in bone marrow derived dendritic cells is a positive regulator of T cell activation
Journal of Translational Medicine volume 10, Article number: P19 (2012)
After a completed T cell response the activation of DCs needs to be terminated to avoid harmful inflammation or autoimmune disease. Besides the negative regulation of JAK/STAT signaling pathway on growth hormone and prolactin for suppressor of cytokine signaling (SOCS) 2 , murine SOCS2-/- DCs are recently found to be hyper-responsive to microbial stimuli and refractory to the inhibitory actions of the anti-inflammatory mediator LXA4 . Thus, we investigate the role of SOCS2 in DC antigen presentation.
Materials and methods
Mice: SOCS2 deficient mice and transgenic OT-II mice. Mouse bone marrow-derived dendritic cells (BMDCs): Mouse bone marrow cells were incubated 7 days with 20 ng/ml GM-CSF and 20 ng/ml IL-4 to create mouse BMDCs. Quantitative RT-PCR: Real-time PCR was used to measure pro-inflamatory cytokines gene expression. CFSE proliferation assay: BMDCs were incubated with 100 ng/ml LPS and 50 ng/ml OVA323-339 peptide. The next day CD90+ splenocytes from OT-II mice were labeled with CFSE and added to the BMDC culture for 5 days. Then cells were stained for CD4 and read by FACS.
Increased production of pro-inflammatory cytokines by SOCS2-/- BMDCs in response to LPS (see Figure 1)
SOCS-/- BMDCs have a decreased capacity to activate naïve CD4+ T cells (see Figure 2)
SOCS2 is complex regulator of DC effecter functionality, with an overall positive regulatory function on T cell activation.
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Machado FS, Johndrow JE, Esper L, Dias A, Bafica A: Anti-inflammatory actions of lipoxin A4 and aspirin-triggered lipoxin are SOCS-2 dependent. Nat Med. 2006, 12: 330-334. 10.1038/nm1355.
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Hu, J., Carow, B., Wikström, AC. et al. SOCS2 expression in bone marrow derived dendritic cells is a positive regulator of T cell activation. J Transl Med 10, P19 (2012). https://doi.org/10.1186/1479-5876-10-S3-P19
- Mouse Bone Marrow
- Cytokine Gene Expression
- SOCS2 Expression
- Mouse Bone Marrow Cell