Cytokines are small proteins that act as messengers between immune cells, orchestrating the body’s defense system. Type 2 cytokines represent a specific group of these messengers, playing a particular role in a distinct type of immune response. They are a subset of interleukins, which are a broader category of cytokines involved in various immune processes.
The Immune Team: Producers and Responders
Type 2 cytokines are produced and responded to by various immune cells. T helper 2 (Th2) cells are a significant source, orchestrating the humoral, or antibody-mediated, immune response. Innate lymphoid cells type 2 (ILC2s) also produce large amounts of Type 2 cytokines, responding rapidly to certain triggers without prior exposure to a specific antigen.
Mast cells, eosinophils, and basophils also contribute. These granulocytes swiftly release substantial amounts of Type 2 cytokines when activated. Epithelial cells, which line body surfaces, can also produce “alarmin” cytokines like thymic stromal lymphopoietin (TSLP), IL-25, and IL-33. These then activate ILC2s and other immune cells to produce Type 2 cytokines.
Their Main Job: Orchestrating Specific Immune Responses
Type 2 cytokines primarily coordinate immune responses in two main areas: defending against parasitic infections and driving allergic reactions. When the body encounters multicellular parasites like worms, Type 2 cytokines, including IL-4, IL-5, and IL-13, become highly active. These cytokines promote a “weep and sweep” response in the gut mucosa, increasing fluid and mucus production, stimulating smooth muscle contraction, and aiding in parasite expulsion. They also activate eosinophils, specialized white blood cells that can directly attack these larger pathogens.
These cytokines are also central to allergic and atopic responses. IL-4 and IL-13, for instance, stimulate B cells to produce immunoglobulin E (IgE) antibodies, which are heavily involved in allergic reactions. These antibodies bind to mast cells, leading to their activation and the release of histamine and other inflammatory substances, which cause common allergy symptoms like inflammation in the airways or skin. IL-5 specifically recruits and activates eosinophils, contributing to the inflammation seen in allergic conditions.
When Things Go Wrong: Type 2 Cytokines and Disease
An overactive or unregulated Type 2 immune response, driven by these cytokines, can contribute to various chronic diseases. In asthma, Type 2 inflammation plays a significant role in airway inflammation, leading to symptoms such as mucus overproduction and bronchoconstriction, which is the narrowing of airways. Specifically, IL-4, IL-5, and IL-13 contribute to this inflammation, affecting lung function.
Allergic rhinitis, commonly known as hay fever, also involves Type 2 inflammation, which can worsen symptoms by causing swelling and excessive mucus in the nasal passages. Atopic dermatitis, or eczema, is another condition where Type 2 inflammation, particularly involving IL-4 and IL-13, contributes to skin inflammation, intense itching, and a compromised skin barrier. These cytokines can reduce the production of filaggrin, a protein important for skin barrier function.
Food allergies also involve Type 2 cytokines, leading to an overreaction of the immune system to certain food components. The dysregulation of these cytokines can lead to severe and sometimes chronic symptoms across these conditions.
Targeting Type 2 Cytokines in Medical Treatments
Understanding the role of Type 2 cytokines has led to the development of new therapeutic strategies. Biologics can precisely target these cytokines or their receptors. These treatments often involve monoclonal antibodies that specifically block the activity of individual Type 2 cytokines, such as IL-4, IL-5, or IL-13, or their receptors.
For example, some biologics are designed to block the IL-4 receptor alpha (IL-4Rα), thereby inhibiting both IL-4 and IL-13 signaling pathways, which are central to Type 2 inflammation. Other biologics target IL-5 or its receptor, reducing the number and activity of eosinophils, significant contributors to inflammation in certain diseases.
These precision treatments are used in conditions like severe asthma, atopic dermatitis, and chronic rhinosinusitis with nasal polyps.