Role of Suppressor of cytokine signaling 2 during the development and resolution of an experimental arthritis

Cramer, Allysson; Galvão, Izabela; Sá, Nathália Venturini de; Gaio, Paulo; Oliveira, Natália Fernanda de Melo; Santos, Mariana Rates Gonzaga; Campolina-Silva, Gabriel Henrique; Valiate, Bruno Vinicius Santos; Souza, Fernanda Rezende; Cassali, Geovanni Dantas; Teixeira, Mauro Martins; Amaral, Flávio Almeida; Machado, Fabiana S.

doi:10.1016/j.cellimm.2021.104476

Cited by 3 publications

(1 citation statement)

References 64 publications

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“…The suppressors of the cytokine signaling (SOCS) family are major negative feedback regulators of inflammation that function through the JAK/STAT pathway [ 13 , 14 ]. Previous reports have identified a role for specific CLRs such as Dectin-1 in inducing SOCS proteins [ 15 , 16 ].…”

Section: Resultsmentioning

confidence: 99%

SOCS3 Regulates Dectin-2-Induced Inflammation in PBMCs of Diabetic Patients

Haider

Albaqsumi

Al-Mulla

et al. 2022

Cells

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The C-type lectin receptors (CLRs) Dectin-1 and Dectin-2 are involved in several innate immune responses and are expressed mainly in dendritic cells, monocytes, and macrophages. Dectin-1 activation exacerbates obesity, inflammation, and insulin resistance/type 2 diabetes (T2D). However, the role of Dectin-2 is not clear in T2D. This study aims to evaluate the expression and function of Dectin-2 in peripheral blood mononuclear cells (PBMCs) isolated from diabetic patients and non-diabetic controls. Flow-cytometry and qRT-PCR were performed to evaluate the expression of Dectin-2 in different leukocyte subpopulations isolated from T2D patients (n = 10) and matched non-diabetic controls (n = 11). The functional activity of Dectin-2 was identified in PBMCs. CRP, IL-1β, and TNF-α concentrations were determined by ELISA. siRNA transfection and Western blotting were performed to assess p-Syk and p-NF-kB expression. siRNA transfection was performed to knock down the gene of interest. Our results show that Dectin-2 expression was the highest in monocytes compared with other leukocyte subpopulations. The expression of Dectin-2 was significantly increased in the monocytes of T2D patients compared with non-diabetic controls. Dectin-2 expression positively correlated with markers of glucose homeostasis, including HOMA-IR and HbA1c. The expression of inflammatory markers was elevated in the PBMCs of T2D patients. Interestingly, SOCS3, a negative regulator of inflammation, was expressed significantly lowlier in the PBMCs of T2D patients. Moreover, SOCS3 expression was negatively correlated with Dectin-2 expression level. The further analysis of inflammatory signaling pathways showed a persistent activation of the Dectin-2-Syk-NFkB pathway that was instigated by the diminished expression of SOCS3. Dectin-2 activation failed to induce SOCS3 expression and suppress subsequent inflammatory responses in the PBMCs of diabetic patients. siRNA-mediated knockdown of SOCS3 in PBMCs displayed a similar inflammatory phenotype to diabetic PBMCs when exposed to Dectin-2 ligands. Altogether, our findings suggest that elevated Dectin-2 and its relationship with SOCS3 could be involved in the abnormal immune response observed in T2D patients.

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Section: Resultsmentioning

confidence: 99%

SOCS3 Regulates Dectin-2-Induced Inflammation in PBMCs of Diabetic Patients

Haider

Albaqsumi

Al-Mulla

et al. 2022

Cells

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SOCS2 regulates alveolar bone loss in Aggregatibacter actinomycetemcomitans-induced periodontal disease

et al. 2023

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The loss-of-function of SOCS2 increases the inflammatory response toStaphylococcus aureusinfection

Guzylack-Piriou,

Gausseres,

Tasca

et al. 2023

Preprint

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The involvement of suppressor of cytokine signaling (SOCS)2 in anti-infective bacterial immunity remains largely undetermined compared to other members of the SOCS family. We developed a mouse model expressing the loss of function R96C SOCS2 point mutation to characterize the response of macrophages to Staphylococcus aureus and its TLR-ligand derivatives. The model resumes observations of gigantism done in Socs2-/- mice. Stimulation of bone-marrow-derived macrophages with various TLR-2 ligands showed upregulation of the pro-inflammatory cytokines IL-6 and TNF-a production only in cytokine-modulating environments that promote SOCS2 expression. Using this model, we showed that SOCS2 protein reduces STAT-5 phosphorylation in a short time frame upon TLR engagement. When SOCS2 is ablated, neutrophil and F4/80int Ly6C+ inflammatory macrophage recruitment, as well as IFN-g and IL-10 concentrations are significantly increased upon S. aureus peritoneal infection. By lowering the pro-inflammatory environment, SOCS2 favors better healing during a systemic infection caused by S. aureus.

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Role of Suppressor of cytokine signaling 2 during the development and resolution of an experimental arthritis

Cited by 3 publications

References 64 publications

SOCS3 Regulates Dectin-2-Induced Inflammation in PBMCs of Diabetic Patients

SOCS3 Regulates Dectin-2-Induced Inflammation in PBMCs of Diabetic Patients

SOCS2 regulates alveolar bone loss in Aggregatibacter actinomycetemcomitans-induced periodontal disease

The loss-of-function of SOCS2 increases the inflammatory response toStaphylococcus aureusinfection

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