Loading…
Group 2 innate lymphoid cells (ILC2s) are pivotal in the immune system's response to various extracellular pathogens, particularly those affecting the bowel. These cells facilitate critical physiological responses such as vasodilation, increased mucus production, and enhanced macrophage activity. ILC2s are characterized by the expression of phenotypic markers such as CD25+, CD127+, and Thy1.2+, and transcription factors like GATA3 and RAR-related orphan receptor alpha (ROR-alfa).
ILC2s are stimulated by cytokines including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP), leading to the secretion of signature cytokines such as IL-4, IL-5, IL-9, IL-13, and amphiregulin (AREG). These cytokines play a crucial role in mediating type 2 inflammatory responses, which are essential for tissue repair and combating infections. For instance, in response to helminth infections, IL-25 further activates ILC2s to produce IL-13, which promotes the differentiation of epithelial crypt progenitors into tuft and goblet cells in the small intestine, aiding in tissue repair and pathogen clearance.
Moreover, ILC2s can undergo transdifferentiation into ILC1s in the presence of cytokines like IL-1 beta, IL-12, and IL-18. This flexibility allows them to adapt to changing immune challenges. Conversely, cytokines such as IL-1 beta, IL-23, IL-6, and TGF-beta can drive the conversion of ILC2s toward ILC3s, demonstrating their versatile role in immune regulation.
In pathological conditions, such as infections by Clostridioides difficile, toxins like TcdA and TcdB induce epithelial cell damage, leading to the release of IL-33. This, in turn, activates ILC2s to secrete IL-5, facilitating the recruitment of eosinophils and supporting epithelial repair. Similarly, in a mouse model of intestinal injury, ILC2s mediated tissue protection by limiting inflammation and promoting epithelial repair through the secretion of amphiregulin.
ILC2s also express receptors like IL-33R and IL-25R, which are crucial for their activation and function. They have been shown to express molecules such as ICOSL and OX40L, which may facilitate cellular contact with T cells, further integrating them into the broader immune response.
The primary function of ILC2s is to promote type 2 inflammation, which is critical in responses to allergies, infections, and tissue repair. They achieve this by secreting cytokines like IL-5 and IL-13, under the regulation of the master transcription factor GATA-3, although they produce relatively low levels of IL-4.
Overall, the diverse functions and regulatory mechanisms of ILC2s highlight their importance in maintaining immune homeostasis and responding to environmental challenges. Their ability to shift between different functional states allows for a dynamic response to infections and injuries, making them a crucial component of the immune system.
References:
Human Group 2 ILCs (ILC2) cells can be found in many different tissues. Even though they generally look the same, they can have unique features depending on the tissue. The proteins CRTH2 / Prostaglandin DP2 receptor, Killer cell lectin-like receptor subfamily G member 1 (KLRG1), CD117, CD49a, CD278 (Inducible T-cell costimulator (ICOS))(brain://sV54NK5RgEeiAweic6cJMQ/InducibleTcellCoStimulatorIcosCd278), CD69, NKp30, CD25, C-C Chemokine Receptor Type 6 (CCR6), C-C Chemokine Receptor Type 4 (CCR4), Interleukin 1 receptor-like 1 (IL1RL1), and Interleukin-17 receptor B (IL-17RB) can be expressed differently in various tissues.
see also:
GATA Binding Protein 3 (GATA3) & Group 2 ILCs (ILC2)
Group 2 ILCs (ILC2) & Interleukin-10 (IL-10)
Group 2 ILCs (ILC2) & Interleukin-13 (IL-13)
Group 2 ILCs (ILC2) & Interleukin-17E (IL-17E) / Interleukin-25 (IL-25)
Group 2 ILCs (ILC2) & Interleukin-33 (IL-33)
Group 2 ILCs (ILC2) & Interleukin-4 (IL-4)
Group 2 ILCs (ILC2) & Interleukin-5 (IL-5)
Group 2 ILCs (ILC2) & Interleukin-9 (IL-9)