Role of IL-6 in the commitment of T cell subsets

Korn, Thomas; Hiltensperger, Michael

doi:10.1016/j.cyto.2021.155654

Cited by 52 publications

(41 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…STAT3 plays an important role in solid tumors, including in KRAS-induced pancreatic tumorigenesis ( Corcoran et al, 2011 ). IL-6 is an important canonical activator of STAT3 and the IL-6/STAT3 axis promotes the expansion of immunosuppressive cells while altering the balance of T-cell subsets ( Mace et al, 2018 ; Korn & Hiltensperger, 2021 ). Notably, IL-6 and activated pY705-STAT3 are evident in CAFs in human PDAC samples and isolated CAFs ( Mace et al, 2018 ); however, the role of STAT3 signaling from CAFs within the context of de novo pancreatic tumorigenesis is unknown.…”

Section: Introductionmentioning

confidence: 99%

STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer

et al. 2022

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is associated with an incredibly dense stroma, which contributes to its recalcitrance to therapy. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types within the PDAC stroma and have context-dependent regulation of tumor progression in the tumor microenvironment (TME). Therefore, understanding tumor-promoting pathways in CAFs is essential for developing better stromal targeting therapies. Here, we show that disruption of the STAT3 signaling axis via genetic ablation of Stat3 in stromal fibroblasts in a KrasG12D PDAC mouse model not only slows tumor progression and increases survival, but re-shapes the characteristic immune-suppressive TME by decreasing M2 macrophages (F480+CD206+) and increasing CD8+ T cells. Mechanistically, we show that loss of the tumor suppressor PTEN in pancreatic CAFs leads to an increase in STAT3 phosphorylation. In addition, increased STAT3 phosphorylation in pancreatic CAFs promotes secretion of CXCL1. Inhibition of CXCL1 signaling inhibits M2 polarization in vitro. The results provide a potential mechanism by which CAFs promote an immune-suppressive TME and promote tumor progression in a spontaneous model of PDAC.

show abstract

Section: Introductionmentioning

confidence: 99%

STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Unfortunately, anti-TNF therapy failed to provide significant protective effect in clinical trials [ 17 ], even though no complications were reported [ 18 , 19 ]. IL-6, on the other hand, orchestrates differentiation and commitment of different T-cell subsets, especially Th17-cells [ 20 ]. Th17-cells are the gatekeepers of mucosal homeostasis and are involved in neutrophil recruitment, thus, contributing to severe asthma [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Combining IL-6 and TNF Blockade in a Mouse Model of Allergic Asthma

Namakanova

Горшкова

Зварцев

et al. 2022

IJMS

View full text Add to dashboard Cite

Combined anti-cytokine therapy is a promising therapeutic approach for uncontrolled steroid-resistant asthma. In this regard, simultaneous blockade of IL-4 and IL-13 signaling by Dupilumab (anti-IL-4Ra monoclonal antibody) was recently approved for severe eosinophilic asthma. However, no therapeutic options for neutrophilic asthma are currently available. Recent advances in our understanding of asthma pathogenesis suggest that both IL-6 and TNF may represent potential targets for treatment of severe neutrophilic asthma. Nevertheless, the efficacy of simultaneous pharmacological inhibition of TNF and IL-6 in asthma was not yet studied. To evaluate the potency of combined cytokine inhibition, we simultaneously administrated IL-6 and TNF inhibitors to BALB/c mice with HDM-induced asthma. Combined IL-6/TNF inhibition, but not individual blockade of these two cytokines, led to complex anti-inflammatory effects including reduced Th2-induced eosinophilia and less prominent Th17/Th1-mediated neutrophilic infiltrate in the airways. Taken together, our results provide evidence for therapeutic potential of combined IL-6/TNF inhibition in severe steroid-resistant asthma.

show abstract

“…Our hypothesis is based on previous research in mice that indicates that Salmonella -specific Th17 cells can recognize Salmonella flagellin ( Lee et al, 2012 ) and that Salmonella Flagellin antigen has also shown an intrinsic ability to elicit IL-1 and IL-6 production ( Salazar-Gonzalez and McSorley, 2005 ; Mizel and Bates, 2010 ). Moreover, it has been reported that IL-6 is a non-redundant differentiation factor for Th17 cells ( Korn and Hiltensperger, 2021 ) in which significantly increased levels of IL-6 can promote the generation of Th17 cells ( Hou et al, 2014 ) and result in IL-6 and IL-17 cytokines. So, the recognition of the vaccine’s flagellin by TLR 5 and its ability to induce significant IL-6 mRNA may be the force driving the Th17 response against Salmonella in the cecal tonsils during S .…”

Section: Discussionmentioning

confidence: 99%

Immunization of Broiler Chickens With a Killed Chitosan Nanoparticle Salmonella Vaccine Decreases Salmonella Enterica Serovar Enteritidis Load

et al. 2022

View full text Add to dashboard Cite

There is a critical need for an oral-killed Salmonella vaccine for broilers. Chitosan nanoparticle (CNP) vaccines can be used to deliver Salmonella antigens orally. We investigated the efficacy of a killed Salmonella CNP vaccine on broilers. CNP vaccine was synthesized using Salmonella enterica serovar Enteritidis (S. Enteritidis) outer membrane and flagella proteins. CNP was stable at acidic conditions by releasing 14% of proteins at pH 5.5. At 17 h post-incubation, the cumulative protein release for CNP was 75% at pH 7.4. Two hundred microliters of PBS with chicken red blood cells incubated with 20 μg/ml CNP released 0% hemoglobin. Three hundred chicks were allocated into 1) Control, 2) Challenge, 3) Vaccine + Challenge. At d1 of age, chicks were spray-vaccinated with PBS or 40 mg CNP. At d7 of age, chicks were orally-vaccinated with PBS or 20 μg CNP/bird. At d14 of age, birds were orally-challenged with PBS or 1 × 107 CFU/bird of S. Enteritidis. The CNP-vaccinated birds had higher antigen-specific IgY/IgA and lymphocyte-proliferation against flagellin (p < 0.05). At 14 days post-infection, CNP-vaccinated birds reversed the loss in gut permeability by 13% (p < 0.05). At 21 days post-infection, the CNP-vaccinated birds decreased S. Enteritidis in the ceca and spleen by 2 Log10 CFU/g, and in the small intestine by 0.6 Log10 CFU/g (p < 0.05). We conclude that the CNP vaccine is a viable alternative to conventional Salmonella poultry vaccines.

show abstract

Role of IL-6 in the commitment of T cell subsets

Abstract: Graphical abstract

Cited by 52 publications

References 105 publications

STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer

STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer

Therapeutic Potential of Combining IL-6 and TNF Blockade in a Mouse Model of Allergic Asthma

Immunization of Broiler Chickens With a Killed Chitosan Nanoparticle Salmonella Vaccine Decreases Salmonella Enterica Serovar Enteritidis Load

Contact Info

Product

Resources

About