page_title: Innate lymphoid cell
section_title: Helminth infection and tissue repair
hierarchical_section_title: Innate lymphoid cell / Function / Helminth infection and tissue repair
caption_attribution_description: English: The ILCs and their role in tissue repair and regeneration after infection and cellular damage.
context_page_description: Innate lymphoid cells are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors. In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid, and non- lymphoid tissues, and rarely in the peripheral blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis. Characteristics allowing their differentiation from other immune cells include the absence of regular lymphoid morphology, rearranged antigen receptors found on T cells and B cells, and phenotypic markers usually present on myeloid or dendritic cells.
  Based on the difference in developmental pathways, phenotype, and signalling molecules produced, in 2013, ILCs were divided into three groups: 1, 2 and 3, however, after further investigation, we now appreciate five distinct subsets within these groups: NK cells, ILC1s, ILC2s, ILC3s, and LTi cells.
context_section_description: A fundamental property of type 2 immunity, and therefore ILC2 cells, is to deal with oversized organisms, that cannot be digested, such as the helminths. In the intestine, in response to a helminth infection, epithelial cells secrete high levels of IL-25, activating ILC2 cells. ILC2s produce IL-13, which drives the differentiation of additional epithelial cells, via Notch signalling pathways. This instruction allows the tissue to be remodelled to allow for the expulsion of the helminth parasite, and other large pathogens. 
  IL-13 also activates T cells, inducing further physiological responses to expel the parasite. T cells stimulate goblet cell mucus secretion, contraction of smooth muscle, and they secrete signals recruiting mast cells and eosinophils to the site, stimulating B cell proliferation. 
  The infection can lead to tissue damage, due to migration of the helminth. ILC2s have a key role in repairing the tissue damage after infection, by producing ligands such as AREG, for epithelial growth factor receptors, which facilitates differentiation of epithelial cells for tissue repair. This can function to enhance the barrier function of the epithelium and slow pathogen entry.
  In multiple tissue niches, ILCs have a relationship with non- hematopoietic cells such as stromal cells. In the lung, ILC2s have a distinct localization to stromal cells, which release IL-33, and TSLP, promoting ILC2 homeostasis, in both the steady state, and in response to helminth infection, after the helminth has developed in the intestine, and migrated to the lung through the blood. 
  Lung ILC2s are positioned close to blood vessels, to allow recruitment of eosinophils from the blood. In addition, they are also positioned within the airways, where potential pathogens may accumulate. This means they are in close contact with neuroendocrine cells, which activate ILC2s via the release of calcitonin gene-related peptide.  Other studies also confirm the regulation of ILC function via neuronal circuits. 
  In addition, ILC1s and ILC3s release oxygen radicals and lethally damaging enzymes in response to pathogenic infection, causing damage to the host tissue. The repair responses for the tissue are coordinated by the type 2 immune response, after the ILC3s and ILC1s have cleansed the tissue of microbes and debris.
caption: The different ILC subtypes and how they are implicated in tissue repair and regeneration after infection with oversized organs such as helminths.[6]
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