InVivoMAb anti-mouse IL-23 (p19)

Clone Catalog # Category
G23-8 BE0313 InVivoMab Antibodies
$900 - $3250

About InVivoMAb anti-mouse IL-23 (p19)

The G23-8 monoclonal antibody reacts with the p19 subunit of mouse IL-23. IL-23 is a heterodimeric cytokine composed of two disulfide-linked subunits, a p19 subunit that is unique to IL-23, and a p40 subunit that is shared with IL-12. IL-23 is secreted by activated dendritic cells and macrophages. IL-23 has been shown to enhance IFNγ production by memory T cells. Additionally, mouse IL-23 induces the proliferation of memory T cells (but not naive T cells), whereas IL-12 has no effect on memory cells. Mouse IL-23 (but not IL-12) can also activate mouse memory T cells to produce the potent proinflammatory cytokine IL-17. IL-23 has been shown to be upregulated in certain autoimmune diseases and promote immunity in response to some viral and mycobacterial infections. The G23-8 antibody can specifically neutralize IL-23 bioactivity with no effect on IL-12 p70 bioactivity.

InVivoMAb anti-mouse IL-23 (p19) Specifications

Isotype

Rat IgG1, κ

Recommended Isotype Control(s) InVivoMAb rat IgG1 isotype control, anti-horseradish peroxidase(BE0088)
Recommended InVivoPure Dilution Buffer InVivoPure pH 7.0 Dilution Buffer(IP0070)
Immunogen

Insect cell-expressed, recombinant mouse IL-23 heterodimer

Reported Applications
  • in vivo IL-23p19 neutralization
  • in vitro IL-23p19 neutralization
  • Western blot
Formulation
  • PBS, pH 7.0
  • Contains no stabilizers or preservatives
Endotoxin
  • <2EU/mg (<0.002EU/μg)
  • Determined by LAL gel clotting assay
Purity
  • >95%
  • Determined by SDS-PAGE
Sterility

0.2 μM filtered

Production

Purified from tissue culture supernatant in an animal free facility

Purification

Protein G

RRID

AB_2754551

Molecular Weight

150 kDa

Storage

The antibody solution should be stored at the stock concentration at 4°C. Do not freeze.

Application References

InVivoMAb anti-mouse IL-23 (p19) (Clone: G23-8)

 

Calcinotto, A., et al. (2018). "IL-23 secreted by myeloid cells drives castration-resistant prostate cancer." Nature 559(7714): 363-369. PubMed

Patients with prostate cancer frequently show resistance to androgen-deprivation therapy, a condition known as castration-resistant prostate cancer (CRPC). Acquiring a better understanding of the mechanisms that control the development of CRPC remains an unmet clinical need. The well-established dependency of cancer cells on the tumour microenvironment indicates that the microenvironment might control the emergence of CRPC. Here we identify IL-23 produced by myeloid-derived suppressor cells (MDSCs) as a driver of CRPC in mice and patients with CRPC. Mechanistically, IL-23 secreted by MDSCs can activate the androgen receptor pathway in prostate tumour cells, promoting cell survival and proliferation in androgen-deprived conditions. Intra-tumour MDSC infiltration and IL-23 concentration are increased in blood and tumour samples from patients with CRPC. Antibody-mediated inactivation of IL-23 restored sensitivity to androgen-deprivation therapy in mice. Taken together, these results reveal that MDSCs promote CRPC by acting in a non-cell autonomous manner. Treatments that block IL-23 can oppose MDSC-mediated resistance to castration in prostate cancer and synergize with standard therapies.

 

Costa, S., et al. (2017). "Role of MyD88 signaling in the imiquimod-induced mouse model of psoriasis: focus on innate myeloid cells." J Leukoc Biol 102(3): 791-803. PubMed

Psoriasis is a chronic skin disease associated with deregulated activation of immune cells and keratinocytes. In this study, we used the imiquimod (IMQ)-induced mouse model of psoriasis to dissect better the contribution of hematopoietic and skin-resident stromal cells to psoriasis development. The comparison of disease development in mice carrying the hematopoietic cell-specific deletion of MyD88 (Myd88(fl/fl)Vav-cre(+) mice) with mice carrying the total MyD88 deficiency (Myd88(-/-) mice), we show that the progression of skin and systemic inflammation, as well as of epidermal thickening, was completely dependent on MyD88 expression in hematopoietic cells. However, both Myd88(-/-) mouse strains developed some degree of epidermal thickening during the initial stages of IMQ-induced psoriasis, even in the absence of hematopoietic cell activation and infiltration into the skin, suggesting a contribution of MyD88-independent mechanisms in skin-resident stromal cells. With the use of conditional knockout mouse strains lacking MyD88 in distinct lineages of myeloid cells (Myd88(fl/fl)LysM-cre(+) and Myd88(fl/fl)MRP8-cre(+) mice), we report that MyD88 signaling in monocytes and Mvarphi, but not in neutrophils, plays an important role in disease propagation and exacerbation by modulating their ability to sustain gammadelta T cell effector functions via IL-1beta and IL-23 production. Overall, these findings add new insights into the specific contribution of skin-resident stromal vs. hematopoietic cells to disease initiation and progression in the IMQ-induced mouse model of psoriasis and uncover a potential novel pathogenic role for monocytes/Mvarphi to psoriasis development.

 

Coffelt, S. B., et al. (2015). "IL-17-producing gammadelta T cells and neutrophils conspire to promote breast cancer metastasis." Nature 522(7556): 345-348. PubMed

Metastatic disease remains the primary cause of death for patients with breast cancer. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and their microenvironment. Within this local microenvironment and in distant organs, immune cells and their mediators are known to facilitate metastasis formation. However, the precise contribution of tumour-induced systemic inflammation to metastasis and the mechanisms regulating systemic inflammation are poorly understood. Here we show that tumours maximize their chance of metastasizing by evoking a systemic inflammatory cascade in mouse models of spontaneous breast cancer metastasis. We mechanistically demonstrate that interleukin (IL)-1beta elicits IL-17 expression from gamma delta (gammadelta) T cells, resulting in systemic, granulocyte colony-stimulating factor (G-CSF)-dependent expansion and polarization of neutrophils in mice bearing mammary tumours. Tumour-induced neutrophils acquire the ability to suppress cytotoxic T lymphocytes carrying the CD8 antigen, which limit the establishment of metastases. Neutralization of IL-17 or G-CSF and absence of gammadelta T cells prevents neutrophil accumulation and downregulates the T-cell-suppressive phenotype of neutrophils. Moreover, the absence of gammadelta T cells or neutrophils profoundly reduces pulmonary and lymph node metastases without influencing primary tumour progression. Our data indicate that targeting this novel cancer-cell-initiated domino effect within the immune system--the gammadelta T cell/IL-17/neutrophil axis--represents a new strategy to inhibit metastatic disease.

 

Krause, P., et al. (2015). "IL-10-producing intestinal macrophages prevent excessive antibacterial innate immunity by limiting IL-23 synthesis." Nat Commun 6: 7055. PubMed

Innate immune responses are regulated in the intestine to prevent excessive inflammation. Here we show that a subset of mouse colonic macrophages constitutively produce the anti-inflammatory cytokine IL-10. In mice infected with Citrobacter rodentium, a model for enteropathogenic Escherichia coli infection in humans, these macrophages are required to prevent intestinal pathology. IL-23 is significantly increased in infected mice with a myeloid cell-specific deletion of IL-10, and the addition of IL-10 reduces IL-23 production by intestinal macrophages. Furthermore, blockade of IL-23 leads to reduced mortality in the context of macrophage IL-10 deficiency. Transcriptome and other analyses indicate that IL-10-expressing macrophages receive an autocrine IL-10 signal. Interestingly, only transfer of the IL-10 positive macrophages could rescue IL-10-deficient infected mice. Therefore, these data indicate a pivotal role for intestinal macrophages that constitutively produce IL-10, in controlling excessive innate immune activation and preventing tissue damage after an acute bacterial infection.

 

Wang, X., et al. (2013). "High-mobility group box 1 (HMGB1)-Toll-like receptor (TLR)4-interleukin (IL)-23-IL-17A axis in drug-induced damage-associated lethal hepatitis: Interaction of gammadelta T cells with macrophages." Hepatology 57(1): 373-384. PubMed

Acetaminophen overdose causes acute liver inflammation with neutrophil infiltration; however, the mechanism of damage-associated inflammation has not been elucidated. In this study we found that the HMGB1-TLR4-IL-23-IL-17A axis played a crucial role in acetaminophen-induced infiltration of neutrophils and liver injury. Notably, interleukin (IL)-17A and IL-23 significantly increased after acetaminophen challenge. A neutralizing antibody against IL-17A attenuated the recruitment of neutrophils, accompanied by reduced liver injury. Only IL-17A(+) CD3(+) gammadelta T cell receptor (TCR)(+) cells were significantly increased in the liver, and depletion of gammadelta T cells, but not CD4(+) T cells or natural killer (NK)T cells significantly reduced IL-17A production, attenuated liver injury, and decreased the number of neutrophils in the liver. Furthermore, a neutralizing IL-23 p19 antibody or p40-deficiency significantly decreased the levels of IL-17A and infiltration of neutrophils. After in vitro stimulation, the percentage of IL-17A-producing gammadelta T cells and the levels of supernatant IL-17A from total hepatic lymphocytes or purified gammadelta T cells markedly increased in the presence with IL-23. Importantly, IL-23 and IL-17A were reduced after inhibition of macrophages and could not be induced in Toll-like receptor TLR4(-/-) mice after acetaminophen challenge. Meanwhile, serum high-mobility group box 1 (HMGB1), a damage-associated molecule released from necrotic hepatocytes, increased after acetaminophen challenge, and the HMGB1 inhibitor glycyrrhizin markedly reduced the production of IL-23 and IL-17A and the recruitment of hepatic neutrophils. HMGB1 stimulated the production of IL-23 by TLR4(+/+) but not by TLR4(-/-) macrophages. CONCLUSION: The HMGB1-TLR4-IL-23 pathway in macrophages makes the generation of IL-17-producing gammadelta T cells, which mediates neutrophil infiltration and damage-induced liver inflammation.

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Wakita, D., et al. (2010). "Tumor-infiltrating IL-17-producing gammadelta T cells support the progression of tumor by promoting angiogenesis." Eur J Immunol 40(7): 1927-1937. PubMed

Based on the evidence that IL-17 is a key cytokine involved in various inflammatory diseases, we explored the critical role of IL-17-producing gammadelta T cells for tumor development in tumor-bearing mouse model. IL-17(-/-) mice exhibited a significant reduction of tumor growth, concomitantly with the decrease of vascular density at lesion area, indicating a pro-tumor property of IL-17. Among tumor-infiltrating lymphocytes (TIL), gammadelta T cells were the major cellular source of IL-17. Analysis of TCR repertoires in TIL-gammadelta T cells showed that circulating gammadelta T cells, but not skin resident Vgamma5(+)gammadelta T cells, produced IL-17. Neutralizing antibodies against IL-23, IL-6, and TGF-beta, which were produced within the tumor microenvironment, inhibited the induction of IL-17-producing gammadelta T cells. IL-17 production by tumor-infiltrating gammadelta T cells was blocked by anti-gammadeltaTCR or anti-NKG2D antibodies, indicating that these ligands, expressed within the tumor microenvironment, are involved in gammadelta T-cell activation. The IL-17-producing TIL-gammadelta T cells exhibited reduced levels of perforin mRNA expression, but increased levels of COX-2 mRNA expression. Together, our findings support the novel concept that IL-17-producing gammadelta T cells, generated in response to tumor microenvironment, act as tumor-promoting cells by inducing angiogenesis.

 

Ivanov, S., et al. (2007). "Functional relevance of the IL-23-IL-17 axis in lungs in vivo." Am J Respir Cell Mol Biol 36(4): 442-451. PubMed

It is known that interleukin (IL)-23, an IL-12-family cytokine, can be released by certain antigen-presenting cells in response to bacterial pathogens. Recent in vitro studies indicate that this cytokine stimulates a unique subset of CD4 cells, the T helper cell (Th)17 subset, to produce and release the proinflammatory cytokine IL-17. However, it has not been known whether this is an action of IL-23 per se that has bearing for the early innate response in lungs in vivo and whether there is an IL-23-responsive population of IL-17-producing CD4 cells in the bronchoalveolar space. We now present evidence that IL-23 can be involved in the early innate response to both gram-negative and gram-positive bacterial products in the lungs: Recombinant IL-23 protein per se accumulates inflammatory cells in the bronchoalveolar space in part via endogenous production of IL-17, and this IL-17 production occurs locally in IL-23-responsive CD4 cells. This IL-17 response to IL-23 occurs without any pronounced impact on Th1/Th2 polarization. Moreover, recombinant IL-23 protein increases the local MMP-9 activity, which is generated by neutrophils mainly. CD4 cells in the lungs may thus respond to IL-23 from antigen-presenting cells exposed to gram-negative and gram-positive pathogens and thereby reinforce the early innate response. These findings support that IL-23 and IL-17 form a functionally relevant "immunological axis" in the lungs in vivo.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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