The mechanism of Tyk2 deficiency-induced immunosuppression in mice involves robust IL-10 production in macrophages.

08:00 EDT 21st March 2020 | BioPortfolio

Summary of "The mechanism of Tyk2 deficiency-induced immunosuppression in mice involves robust IL-10 production in macrophages."

Macrophages are highly plastic in their pro-inflammatory/anti-inflammatory roles. Type I and II interferons (IFNs) are known to modulate macrophage activation. Tyrosine kinase 2 (Tyk2) has an intimate relationship with type I and II IFN signaling. Animal studies have shown that Tyk2 knock-out (KO) in mice is associated with reduced inflammatory responses in various mouse models of diseases. To investigate the role of Tyk2 in inflammation in more detail, we intraperitoneally injected heat-killed Propionibacterium acnes (P. acnes) to Tyk2 KO mice. P. acnes-induced acute peritoneal inflammation, assessed by neutrophil infiltration, was reduced in Tyk2 KO mice. The reduction was accompanied with diminished productions of inflammatory cytokines and an enhanced production of anti-inflammatory IL-10. Unexpectedly, pre-treatment of wild-type mice with the neutralizing antibodies for IFNs did not affect P. acnes-induced neutrophil infiltration. A neutralizing antibody for the IL-10 receptor in Tyk2 KO mice restored P. acnes-induced peritoneal inflammation. Enhanced production of IL-10 from Tyk2 KO peritoneal cells was suppressed by either the cyclooxygenase inhibitor diclofenac or protein kinase A inhibitor H-89. The level of prostaglandin E (PGE) in the steady-state peritoneal cavity in Tyk2 KO mice was higher than that in wild-type mice. Tyk2 KO macrophages showed an enhanced CREB phosphorylation induced by P. acnes plus PGE. Taken together, these results showed that Tyk2 deficiency potentiates the PGE-protein kinase A-IL-10 pathway in macrophages, and thereby contributes to potentiation of the immunosuppressive phenotype.


Journal Details

This article was published in the following journal.

Name: Cytokine
ISSN: 1096-0023
Pages: 155077


DeepDyve research library

PubMed Articles [23612 Associated PubMed Articles listed on BioPortfolio]

Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin-induced pulmonary neutrophil recruitment and neutrophil extracellular trap (NET) formation.

Pulmonary immunosuppression often occurs after burn injury (BI). However, the reasons for BI-induced pulmonary immunosuppression are not clearly understood. Neutrophil recruitment and neutrophil extra...

PAI-1 is involved in delayed bone repair induced by glucocorticoids in mice.

Glucocorticoid (GC) treatments induce osteoporosis and chronic GC treatments have been suggested to induce delayed bone repair; however, the mechanisms by which GC induces delayed bone repair remain u...

Reproduction-related proteins differentially expressed in the testes of the mice with kidney-yang or kidney-yin deficiency.

To compare the differentially expressed proteins in mice with kidney-yang deficiency and those with kidney-yin deficiency induced by hydrocortisone, and explore the similar and different material base...

Autophagy plays a critical role in Klotho gene deficiency-induced arterial stiffening and hypertension.

Klotho is an anti-aging gene that shortens the life span when disrupted and extends the lifespan when overexpressed. This study investigated whether autophagy plays a role in Klotho gene deficiency-in...

Beneficial effect of Sepia esculenta ink polysaccharide on cyclophosphamide-induced immunosuppression and ovarian failure in mice.

In order to investigate prevention of squid ink polysaccharide (SIP) against cyclophosphamide (CP) induced ovarian failure and immunosuppression in mice, female Kunming mice were subjected to intraper...

Clinical Trials [8376 Associated Clinical Trials listed on BioPortfolio]

Photodynamic Therapy-Induced Immune Modulation: Part III

This study is designed as a double-blinded proof of concept of feasibility study to define if the immunosuppression associated with photodynamic therapy (PDT) can be blocked by treatment w...

CLCF1 Gene Associated With Postmenopausal Osteoporosis of Kidney Yin Deficiency Syndrome

For nearly 112 million patients with osteoporosis in China, it is of great significance for preventing and treating by clearly understanding the molecular mechanism of kidney deficiency. T...

Safety Outcomes of Lower Immunosuppression Versus Traditional Immunosuppression in Heart Transplant Recipients

This is a study to compare less intense immunosuppression with a more traditional approach. The hypothesis is that less immunosuppression will provide similar protection against rejection ...

Evaluation of Sepsis-induced Immunosuppression Base on QuantiFERON Monitor® in Septic Shock

QuantiFERON Monitor® is an immunological test evaluating the nonspecific cellular response by measuring interferon gamma (IFNγ) secretions after T-cell and natural killer lymphocyte stim...

Demonstration of the Prebiotic-like Effects of Camu-camu Consumption Against Obesity-related Disorders in Humans

Previous work of the investigators demonstrated the anti-obesity and anti-steatosis potential of the Amazonian fruit camu-camu (CC) in a mouse model of diet-induced obesity [1]. It was dem...

Medical and Biotech [MESH] Definitions

Species of GAMMARETROVIRUS, containing many well-defined strains, producing leukemia in mice. Disease is commonly induced by injecting filtrates of propagable tumors into newborn mice.

Immunosuppression by the administration of increasing doses of antigen. Though the exact mechanism is not clear, the therapy results in an increase in serum levels of allergen-specific IMMUNOGLOBULIN G, suppression of specific IgE, and an increase in suppressor T-cell activity.

A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.

Acquired defect of cellular immunity that occurs in mice infected with mouse leukemia viruses (MuLV). The syndrome shows striking similarities with human AIDS and is characterized by lymphadenopathy, profound immunosuppression, enhanced susceptibility to opportunistic infections, and B-cell lymphomas.

A species of ORTHOPOXVIRUS infecting mice and causing a disease that involves internal organs and produces characteristic skin lesions.

Quick Search

DeepDyve research library

Relevant Topic

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Searches Linking to this Article