Regulation of innate immunity by suppressor of cytokine signaling (SOCS) proteins

Dalpke, Alexander H.; Heeg, Klaus; Bartz, Holger; Baetz, Andrea

doi:10.1016/j.imbio.2007.10.008

Cited by 158 publications

(135 citation statements)

References 68 publications

(73 reference statements)

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…Therefore, the exacerbated disease phenotype of the STING-deficient MRL/lpr mice likely results from the failure to constrain aberrantly activated TLR signaling cascades responsible for disease. Intriguingly, A20-, SOCS1-, or SOCS3-deficient mice exhibit phenotypes similar to our STING/lpr mice (30,31). In addition to impaired expression of these negative regulators of TLR activation, STING/lpr mice also failed to express the secreted immunosuppressive protein IDO-1.…”

Section: Discussionsupporting

confidence: 70%

Suppression of systemic autoimmunity by the innate immune adaptor STING

Sharma

Campbell

Chan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

149

139

View full text Add to dashboard Cite

Cytosolic DNA-sensing pathways that signal via Stimulator of interferon genes (STING) mediate immunity to pathogens and also promote autoimmune pathology in DNaseII- and DNaseIII-deficient mice. In contrast, we report here that STING potently suppresses inflammation in a model of systemic lupus erythematosus (SLE). Lymphoid hypertrophy, autoantibody production, serum cytokine levels, and other indicators of immune activation were markedly increased in STING-deficient autoimmune-prone mice compared with STING-sufficient littermates. As a result, STING-deficient autoimmune-prone mice had significantly shorter lifespans than controls. Importantly, Toll-like receptor (TLR)-dependent systemic inflammation during 2,6,10,14-tetramethylpentadecane (TMPD)-mediated peritonitis was similarly aggravated in STING-deficient mice. Mechanistically, STING-deficient macrophages failed to express negative regulators of immune activation and thus were hyperresponsive to TLR ligands, producing abnormally high levels of proinflammatory cytokines. This hyperreactivity corresponds to dramatically elevated numbers of inflammatory macrophages and granulocytes in vivo. Collectively these findings reveal an unexpected negative regulatory role for STING, having important implications for STING-directed therapies.

show abstract

Section: Discussionsupporting

confidence: 70%

Suppression of systemic autoimmunity by the innate immune adaptor STING

Sharma

Campbell

Chan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

149

139

View full text Add to dashboard Cite

show abstract

“…It was also noted that recovery of IB␣ to basal levels appeared to occur more quickly; this phenomenon is similar to that of IRAK-M knock-outs, IRAK-M also being known as a negative regulator of MyD88-mediated signaling (23). The quick recovery may be due to faster activation of the negative feedback system, which is mediated by suppressors of cytokine signaling (SOCS) proteins (24).…”

Section: Nrx Synergistically Inhibits the Tlr4/myd88mentioning

confidence: 65%

Nucleoredoxin Negatively Regulates Toll-like Receptor 4 Signaling via Recruitment of Flightless-I to Myeloid Differentiation Primary Response Gene (88)

Hayashi

Funato

Terabayashi

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…Consequently, SOCS1 induction was lost as also observed for direct ERK inhibition. Confirming these observations, MAPKs have been shown to trigger SOCS transcription (2,8,43), although ERK specifically had not been analyzed in detail so far. The exact mechanism by which Pyk2 regulates ERK and subsequent SOCS1 expression is still unclear, but previous work has shown that in other cell types, Syk and Pyk2 can activate ERK via either the Ras-Raf pathway or the MAPKKK Tpl2 (44,45).…”

Section: Discussionmentioning

confidence: 98%

Dectin-1 Stimulation Induces Suppressor of Cytokine Signaling 1, Thereby Modulating TLR Signaling and T Cell Responses

Eberle

Dalpke

2012

The Journal of Immunology

View full text Add to dashboard Cite

Suppressor of cytokine signaling (SOCS) proteins serve as negative regulators of cytokine receptor signaling. However, SOCS proteins are not only induced via the JAK/STAT pathway, but are also transcribed on triggering of pattern recognition receptors such as TLRs. We now show that SOCS1 can also be induced by the non-TLR pattern recognition receptor Dectin-1 in murine bone marrow-derived dendritic cells and macrophages (BMMs). The C-type lectin Dectin-1 binds to yeasts and signals either in an autonomous manner or can be triggered in combination with TLRs. In our study, SOCS1 was expressed independently of any TLR engagement as a direct target gene of the Dectin-1 ligand Zymosan. Induction of SOCS1 was mediated by a novel pathway encompassing the tyrosine kinases Src and Syk that activated the downstream kinase proline-rich tyrosine kinase 2. Proline-rich tyrosine kinase 2, in turn, caused activation of the MAPK ERK, thereby triggering SOCS1 induction. SOCS1 did not modulate Dectin-1 signaling but affected TLR signaling, leading to decreased and abbreviated NF-κB activation in BMMs triggered by TLR9. Furthermore, IL-12 and IL-10 secretion were inhibited by SOCS1. We additionally observed that IL-17–producing Th cells were clearly increased by SOCS1 in BMMs. Our results show that SOCS1 is expressed via a new, NF-κB–independent pathway in Dectin-1–triggered murine BMMs and influences TLR cross talk and T cell priming.

show abstract

Regulation of innate immunity by suppressor of cytokine signaling (SOCS) proteins

Cited by 158 publications

References 68 publications

Suppression of systemic autoimmunity by the innate immune adaptor STING

Suppression of systemic autoimmunity by the innate immune adaptor STING

Nucleoredoxin Negatively Regulates Toll-like Receptor 4 Signaling via Recruitment of Flightless-I to Myeloid Differentiation Primary Response Gene (88)

Dectin-1 Stimulation Induces Suppressor of Cytokine Signaling 1, Thereby Modulating TLR Signaling and T Cell Responses

Contact Info

Product

Resources

About