EYRAplex: Human T‑reg (11‑plex)

Chemokine ligand 22 (CCL22), also known as macrophage-derived chemokine (MDC), belongs to the CC chemokine family. CCL22 is mainly secreted by macrophages and dendritic cells and has chemoattractant activity for T cells, dendritic cells, and NK cells. CCL22 is upregulated in certain cancers, infectious diseases, and autoimmune diseases.

CD25 is expressed by activated T cells, B cells, and monocytes. Tregs, responsible for regulating immune tolerance, express the highest amounts of CD25. CD25 is the IL-2 receptor α chain, which functions as one subunit of the high-affinity variant of the IL-2 receptor. When cleaved off by proteases, the soluble receptor (sIL-2Rα) is released extracellularly. Soluble CD25 has a low affinity for IL-2 and can function either as a decoy receptor reducing the activity of IL-2 or by enabling trans presentation to cells expressing the dimeric, intermediate-affinity IL-2R. Increased levels of soluble CD25 indicate ongoing immune responses, and therefore CD25 has been investigated as a biomarker for disease. For example, elevated sCD25 levels have been associated with autoimmune disorders, severe COVID-19, and some types of cancer. 

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 2 (IL-2) is predominantly produced by activated T cells. IL-2 promotes the proliferation, differentiation, and survival of antigen-activated T cells and NK cells. After antigen stimulation, the cytokine also promotes the differentiation of T cells into effector and memory T cells. Therefore IL-2 plays an important role in the body's response to infection. IL-2 is also key to tolerance, as it promotes the differentiation of certain immature T cells into regulatory T cells in the thymus, ultimately preventing autoimmune diseases. 

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.

Perforin is produced by cytotoxic T cells and NK cells as an effector molecule in the cell-mediated destruction of target cells. Perforin is responsible for pore formation and facilitates the delivery of granzymes which induces apoptosis of the target cell.

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).