EYRAplex: Human Th1/Th2 (18‑plex)

CCL3, also known as MIP-1α (Macrophage Inflammatory Protein-1 alpha), is a chemokine primarily secreted by macrophages, dendritic cells, and activated T cells. Its main role in the immune system is to recruit and activate immune cells, particularly monocytes, lymphocytes, and natural killer (NK) cells, to sites of infection or inflammation. CCL3 also enhances immune responses by promoting cytokine production and facilitating cell-to-cell communication, playing a crucial role in both innate and adaptive immunity.

The CCL4 chemokine plays a role in inflammation and chemotaxis. CCL4 is produced by a variety of cells, including monocytes, NK cells, and T cells. It binds to CCR5. This receptor is expressed by T cells and macrophages (among others). CCL4 is involved in the host response to a wide range of pathogens, it's been especially studied in HIV. Furthermore, dysregulation of CCL4 expression has been associated with various pathological conditions, including autoimmune diseases and cancer. CCL4 is also named macrophage inflammatory protein-1β (MIP-1β). 

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. 

Granulocyte macrophage-colony stimulating factor (GM-CSF) can be secreted by T cells, macrophages, endothelial cells, and fibroblasts. GM-CSF stimulates the survival and functional activities of myeloid, that is, monocytes, macrophages, DCs, neutrophils, and eosinophils. It also stimulates the differentiation and proliferation of hematological progenitors.

Granzyme B is a serine protease released by the cytoplasmic granules within cytotoxic T cells and NK cells. Granzyme B will act together with perforin and other cytotoxic mediators to induce target cell death by apoptosis.

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 5 (IL-5) is a pleiotropic cytokine primarily produced by T and NK cells.  IL-5 specifically controls the survival, differentiation, and chemotaxis of eosinophils. But initially, IL-5 was characterized by its ability to support the growth and terminal differentiation of B 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 12 (IL-12) is, when biologically active, a heterodimer (p70) consisting of two covalently linked subunits, p35 and p40. The p40 subunit is shared with IL-23. IL-12 is produced by antigen-presenting cells, specifically dendritic cells, and macrophages. IL-12 is a proinflammatory cytokine that promotes Th1-type responses by inducing IFN-γ production and enhancing the proliferation and cytotoxicity of NK and T cells.

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 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. 
 

Interferon gamma-induced protein 10 (IP-10) secretion is induced by IFN-γ, TNF-α, and IL-1β. This proinflammatory cytokine is produced by monocytes, endothelial cells, and fibroblasts. The interferon gamma-induced protein 10 recruits lymphocytes to sites of infection and increases the expression of MHC class I molecules. In addition to chemotaxis, IP-10 is also involved in the differentiation and activation of peripheral immune cells, regulation of cell growth, apoptosis, and modulation of angiostatic effects. The binding of IP-10 (CXCL10) to the CXCR3 receptor causes the downstream activation of the phospholipase C-dependent pathway, an increase in intracellular calcium production, and actin reorganization. 

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.

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.