Immune cells are among the most perceptive in our bodies—unique in their ability to read their environments and act accordingly. They are experts at integrating various signals within an organism and determining how to act based on these cues. These cues can be broken down into two main camps, one being a “cell-cell interaction” – a handshake between two neighboring cells, and the other being “soluble” signals called cytokines. Cytokines are protein and chemical signals that cells use to communicate with each other. Each type of immune cell, be it a neutrophil or a killer T cell, has cytokine receptors on its surface that engage different types of cytokines and instruct the cell’s functions. In this 101, we’ll very briefly touch upon some types of cytokines encountered in the immune system, and cover them in more depth in subsequent articles.

Chemokines

An important feature of immune cells is their ability to position themselves or migrate to the right place at the right time. Many immune cells use chemokines to find their targets and even position themselves within tissues and organs at steady-state. Chemokines send signals through G-protein coupled receptors (GPCRs), which can allow the cells to remodel their actin cytoskeleton and give them the ability to migrate. Important chemokines in immune signaling are characterized by C-C motif or a C-X-C motif on the protein ligand (chemokine) and the receptor. For example, cells in the lymphatic vessels and lymph node produce chemokines CCL19 and CCL21, which can attract T cells expressing the receptor CCR7 into the lymph node as well as guide them to properly position themselves in the organ long-term. Chemokines can also come in the variety of lipid products such as prostaglandins or leukotrienes, which attract neutrophils to sites of inflammation and tissue damage.

Interleukins

Another class of cytokines are the interleukins, the ubiquitous “IL-(insert number)”s we constantly hear about. Interleukins were classified as signals between leukocytes (thus, “interleukin”) and are quite diverse in their individual properties and functions in immunity. Some of the most commonly encountered interleukin families are the “IL-1 family” and the “common gamma chain” cytokines. Common gamma chain cytokines include IL-7, IL-2, IL-15, which are important for the survival and function of T cells, as well as IL-4, IL-9, and IL-21 which can serve to polarize helper T cells during differentiation. The IL-1 family of cytokines is heavily involved in pro-inflammatory innate immune signaling, as well as maintaining the baseline function of cells in “barrier tissues” like the skin and gut.

Interferons

Interferons (IFN) interfere with viral activity. Type I IFNs can be made in any cell type as a response to viral infection, and inhibit viral replication by activating downstream signaling pathways in a cell. Interferon gamma (IFN-g) is a widely known cytokine produced primarily by cytotoxic and helper T cells, and can signal to other cells in an environment to propagate the immune response. IFN-g, for example, induces production of chemokines and causes dilation of blood vessels that draws other immune cells into a site of infection.

Tumor Necrosis Factors

Tumor Necrosis Factor family members are a class of cytokines critical for inflammatory response, cell death (TNF-α), and the development of the immune system. TNF family members include lymphotoxins, which are critical to the development of lymphoid organs, as well as CD40L, OX-40L, BAFF and others which regulate the differentiation and function of lymphocytes.

Thinking about cytokines and their impact on the immune system can be very complicated even for the most seasoned immunologist. Each cell can have different receptors on its surface at any given time. Sometimes, these receptors integrate competing signals (pro-inflammatory vs. anti-inflammatory) from an environment into a cell. However, we can’t predict how a cell might respond to a particular set of cytokines based merely on the receptors it has on its surface. The machinery within a cell, like complex epigenetic or transcriptional programs, can also impact the decision-making process. We are still trying to understand the various permutations and combinations of cytokine signals that lead to each type of immune function, which is being tackled by scientists from many fascinating angles, including high-throughput screens and disease state modeling. Stay tuned for all of the exciting research to come!

 

Featured Image: Jawahar Swaminathan, EMBL Public Domain

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