Interleukin-10 (IL-10) is an anti-inflammatory cytokine that plays a key role in maintaining immune homeostasis. IL-10-mediated responses are triggered upon binding to a heterodimeric receptor complex consisting of IL-10 receptor (IL-10R)1 and IL-10R2. Engagement of the IL-10R complex activates the intracellular kinases Jak1 and Tyk2, but the exact roles of IL-10R2 and IL-10R2-associated signaling via Tyk2 remain unclear. To elucidate the contribution of IL-10R2 and its signaling to IL-10 activity, we re-evaluated IL-10-mediated responses on bone marrow-derived dendritic cells, macrophages and mast cells. By using bone marrow from IL-10R-/- mice it was revealed that IL-10-mediated responses depend on both IL-10R1 and IL-10R2 in all three cell types. On the contrary, bone marrow-derived cells from Tyk2-/- mice showed similar responses to IL-10 as wild-type cells, indicating that signaling via this IL-10R2-associated kinase only plays a limited role. Tyk2 was shown to control the amplitude of STAT3 activation and the up-regulation of downstream SOCS3 expression. SOCS3 up-regulation was found to be cell-type dependent and correlated with the lack of early suppression of LPS-induced TNF-α in dendritic cells. Further investigation of the IL-10R complex revealed that both the extracellular and intracellular domains of IL-10R2 influence the conformation of IL-10R1 and that both domains were required for transducing IL-10 signals. This observation highlights a novel role for the intracellular domain of IL-10R2 in the molecular mechanisms of IL-10R activation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634637PMC
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186317PLOS

Publication Analysis

Top Keywords

il-10-mediated responses
12
intracellular domain
8
domain il-10r2
8
il-10r1 il-10r2
8
il-10r complex
8
bone marrow-derived
8
dendritic cells
8
il-10r2
7
il-10
5
cells
5

Similar Publications

Ccl2-Induced Regulatory T Cells Balance Inflammation Through Macrophage Polarization During Liver Reconstitution.

Adv Sci (Weinh)

December 2024

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xiamen University, State Key Laboratory of Cellular Stress Biology, Cancer Research Center, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.

Article Synopsis
  • * A study shows that type 1 innate lymphoid cells (ILC1s) are key in producing the inflammatory molecule Ccl2, which recruits other immune cells to aid in liver regeneration.
  • * Regulatory T cells (Tregs) and their production of IL-10 help regulate inflammation by changing macrophages from a pro-inflammatory state (M1) to an anti-inflammatory state (M2), improving liver recovery and balance in the immune response.
View Article and Find Full Text PDF

M-polarized, tumor-associated macrophages (TAMs) produce pro-tumorigenic and angiogenic mediators, such as interleukin-8 (IL-8) and IL-10. Leucine-rich repeat-containing protein 8 members (LRRC8s) form volume-regulated anion channels and play an important role in macrophage functions by regulating cytokine and chemokine production. We herein examined the role of LRRC8A in IL-8 and IL-10 expression in THP-1-differentiated M-like macrophages (M-MACs), which are a useful tool for investigating TAMs.

View Article and Find Full Text PDF

CPT1A-IL-10-mediated macrophage metabolic and phenotypic alterations ameliorate acute lung injury.

Clin Transl Med

August 2024

Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common acute respiratory failure due to diffuse pulmonary inflammation and oedema. Elaborate regulation of macrophage activation is essential for managing this inflammatory process and maintaining tissue homeostasis. In the past decades, metabolic reprogramming of macrophages has emerged as a predominant role in modulating their biology and function.

View Article and Find Full Text PDF

Background: Inflammation is a key pathological process in bacterial meningitis, and the transforming growth factor-beta-activated kinase 1 (TAK1)/nuclear factor-kappa B (NF-κB) pathway is implicated in the activation of microglia and the production of inflammatory factors. Interleukin (IL)-10 is an anti-inflammatory cytokine acting in an autocrine fashion in macrophages to limit inflammatory responses by decreasing the production of pro-inflammatory cytokines. This paper investigates how IL-10 can inhibit microglia activation and reduce the inflammatory response of nervous system diseases.

View Article and Find Full Text PDF

Background: Ovarian cancer (OC), a highly lethal cancer in women, has a 48% 5-year overall survival rate. Prior studies link the presence of IL-17 and Th17 T cells in the tumor microenvironment to improved survival in OC patients. To determine if Th17-inducing vaccines are therapeutically effective in OC, we created a murine model of Th17-inducing dendritic cell (DC) (Th17-DC) vaccination generated by stimulating IL-15 while blocking p38 MAPK in bone marrow-derived DCs, followed by antigen pulsing.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!