EYRAplex: Human Th17/Th22 (13‑plex)

Interferon-γ (IFN-γ) is the only type II interferon. This proinflammatory cytokine is secreted by activated T cells and NK cells. It activates macrophages and endothelial cells and regulates immune responses by affecting APCs, T cells, and B cells. Production of IFN-γ by helper T cells and cytotoxic T cells is a hallmark of the Th1-type phenotype. Thus, high-level production of IFN-γ is typically associated with effective host defense against intracellular pathogens.

Interleukin 1ß (IL-1ß) is a proinflammatory cytokine and inducer of acute phase responses. IL-1ß is produced primarily by monocytes, macrophages, and dendritic cells after induction by microbes.
 

Interleukin 4 (IL-4) is produced primarily by Th2 cells, mast cells, eosinophils, and basophils. IL-4 was first identified to costimulate B cell growth; the cytokine is essential for B cell secretion of IgE and augments the production of IgG1 in vivo. In addition to regulating B cell growth and immunoglobulin secretion, IL-4 also affects T cells. In vitro, IL-4 promotes T cell growth and can induce cytolytic T cell activity. IL-4 also induces the differentiation of naive CD4 T cells into Th2 cells, which are characterized by their capacity to secrete the cytokines IL-4, IL-5, and IL-10 upon activation, while simultaneously inhibiting the generation of Th1 cells.

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by many different cell types and plays a role in a wide range of functions, such as immune responses, acute-phase reactions, and hematopoiesis. Among other things, it augments antibody production from activated B cells in vitro.

Interleukin 10 (IL-10) is a pleiotropic cytokine produced by activated T cells and monocytes. It can modulate the functions of immune responses in both a stimulatory and an inhibitory way. IL-10 is thereby involved in the regulation of immune reactions and inflammatory responses.

Interleukin 13 (IL-13) is produced by Th2-type cells, mast cells, and NK cells in response to activation. It regulates the secretion of IgE by B cells and the Th2-type cell development and suppresses inflammatory responses by regulation of macrophage function.

Interleukin 17A (IL-17A) is a potent proinflammatory cytokine produced by activated Th17 (T helper 17) cells and certain cells belonging to the innate immune system. In mice, IL-17 has also been shown to be produced by activated CD8 T cells and γδ T cells. Th17 cells play an important role in autoimmune diseases and protection against bacteria and fungi. IL-17A acts on a broad range of cell types to induce the expression of cytokines, chemokines, and metalloproteinases. As a result, secretion of IL-17A promotes inflammatory responses, which leads to the recruitment of neutrophils, enhancement of antibody production, and activation of T cells. Increased expression of IL-17A is seen in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. It is also associated with asthma, psoriasis, cancer, and transplant rejection.

Interleukin 17F (IL-17F) is a homodimer composed of two IL-17F subunits. IL17-F is a member of the IL-17A protein family. This proinflammatory cytokine is produced by activated Th17 (T helper 17) cells and certain cells of the innate immune system. Th17 cells play an important role in protection against bacteria and fungi. IL-17F contributes to the pathogenesis of inflammatory and autoimmune diseases, for example, psoriasis.

Interleukin 21 (IL-21) is primarily secreted by CD4 T cells (particularly follicular T cells and Th17) and is an important regulator of immune responses. For Th17 cells, IL-21 is an autocrine regulator sustaining Th17 development. IL-21 also regulates the development of other T cells as well as B cells, NK cells, and dendritic cells. Areas of particular interest for research on IL-21 include autoimmune and inflammatory diseases, cancer research, and basic studies on, e.g., B cells and T cells, especially on Th17 cells.

The cytokine interleukin 22 (IL-22) is mainly produced by activated CD4 T helper 17 (Th17) and T helper 22 (Th22) cells. The IL-22 receptor is expressed on non-immune cells, particularly epithelial cells and keratinocytes, and IL-22 promotes innate immune responses versus bacterial infections in these target cells. In addition, Th22 cells have been shown to play a role in the pathophysiology of several human skin diseases.

Interleukin 31 (IL-31) is a cytokine belonging to the IL-6 family. It is mainly secreted by activated T cells, especially in Th2 helper cells, mast cells, macrophages, and dendritic cells. IL-31 mainly acts in the skin, lung, intestine, and nervous system, facilitating cell-mediated immunity against pathogens. The receptor for IL-31 is found on e.g. keratinocytes and endothelial cells and can be upregulated on activated monocytes. However, IL-31 is considered a Th2-type cytokine with different functions than other Th2-type cytokines. In transgenic mice overexpressing IL-31, the cytokine induces pruritus and dermatitis resembling human atopic dermatitis (AD). In humans, IL-31 has been associated with AD, atopic and contact allergies, airway hypersensitivity, and inflammatory bowel disease. 
 

Transforming growth factor β1 (TGF-β1) is secreted by many cells and controls functions such as cell growth, cell differentiation, proliferation, and apoptosis. The cytokine TGF-β1 is an important regulator of immune functions. Specifically for T cells, TGF-β1 promotes the differentiation of regulatory T cells, preventing IL-1- and IL-2-dependent proliferation of activated T cells, the activation of helper T cells, and cytotoxic T cells. TGF-β1 is secreted in a latent, biologically inactive form, non-covalently linked with a latency associated protein (LAP). 

Tumor necrosis factor (TNF), also known as TNF-α, is produced by many different cell types, e.g., monocytes, macrophages, T cells, and B cells. Among the many effects of TNF-α are protection against bacterial infection, cell growth modulation, immune system regulation, and involvement in septic shock.