What is IL-12 p40?

Abstract. IL-12p40 is known as a component of the bioactive cytokines interleukin (IL)-12 and IL-23 but it is not widely recognized as having intrinsic functional activity. Recent publications have altered this perception and support an independent role for IL-12p40.

What is IL 12p70?

IL-12p70 is a heterodimer composed of p35 and p40 and is a pro-inflammatory cytokine that enhances Th1 (40, 41), cytotoxic CD8+ T (42), and NK (43) cell responses by increasing IFN-γ production (44).

What is p35 and p40?

The genes encoding IL-12 p40 and p35 are located on different human and mouse chromosomes (3). The highly coordinated expression of p40 and p35 genes to form IL-12 (also called p70) in the same cell type at the same time is essential for the initiation of an effective immune response.

What produces IL-23?

IL-23 is mainly secreted by activated dendritic cells, macrophages or monocytes. Innate lymphoid cells and γδ T cells also produce IL-23. B cells produce IL-23 through B cell antigen receptor signaling. Secretion is stimulated by an antigen stimulus recognised by a pattern recognition receptor.

What is il12p70?

Interleukin-12, p70 (IL-12 p70) is a disulfide-linked heterodimeric 70-kDa cytokine composed of a 197 amino acid 35-kDA (p35) subunit and a 306 amino acid 40-kDa (p40) subunit. It is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.

Why did IL-12 IL-23 antibody therapy fail in MS?

Investigators found no clinical or radiologic improvement in any treatment group compared with placebo controls. We consider the known mechanisms of action for IL-12/23 in multiple sclerosis and suggest that ustekinumab’s lack of efficacy was partially due to the study’s inclusion of patients with advanced disease.

Is IL-12 anti-inflammatory?

IL-12 can aid in the activation and regulation of several cytotoxic immune cells including macrophages, natural killer cells, and T cells, thus making it a ‘pro-inflammatory cytokine’.

Does Th17 produce IL-23?

This puts the spotlight on IL-23, which is secreted by skin DCs, and induces production of proinflammatory mediators by Th17 cells such as IL-17A, IL-17F, and IL-22.

What are IL-12 and IL-23?

Interleukin (IL)-12 and IL-23 are important cytokines which are involved in the adaptive immune responses and their common pathway has been found to play a determinant role in the induction of inflammation.

Can stelara treat MS?

STELARA was initiated and more than 80% improvement in her cutaneous lesions was reported 4 months after starting treatment. Scalp lesion flare-ups were controlled with topical medications as needed. During the 4 years of therapy with STELARA, her MS remained stable without progression.

What is the P40 monomer of IL12?

The IL-12 family of molecules has four different members, including p40 monomer (p40), p40 homodimer (p40 2 ), IL-12 (p40:p35), and IL-23 (p40:p19) ( 2, 4 ). In the current era of science, where heterodimers rule, only IL-23 and IL-12 were thought to be biologically active.

Is P40 homodimeric p40 a cytokine?

Homodimeric p40 competes with heterodimer for binding to the high affinity IL-12R and inhibits IL-12 bioactivity in vitro. However, the production and significance of p40 homodimer as a cytokine an …

Does P40 inhibit IL-12 in T cells?

The p40 Suppresses the Internalization of IL-12Rβ1, but Neither IL-12Rβ1 nor IL-23R, in T Cells: Potential Mechanism for the Inhibition of IL-12–, IL-23–, and p40 2 -Mediated Signaling. To understand the mechanism by which p40 attenuated the disease process of EAE, we investigated the effect of p40 on IL-12, IL-23, and p40 2 signaling pathways.

Is nucleosome remodeling at the IL-12 p40 promoter a TLR-dependent or REL-independent event?

Weinmann, A. S. et al. Nucleosome remodeling at the IL-12 p40 promoter is a TLR-dependent, Rel-independent event. Nature Immunol. 2, 51–57 (2001). Hayes, M. P., Wang, J. & Norcross, M. A. Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-γ of lipopolysaccharide-inducible p35 and p40 genes.