The most well-known innate lymphoid cell is the natural killer cell, however more recent developments have shown there are actually numerous ILCs that participate in immunity. These cells are a unique type of lymphocyte that do not express typical B or T lymphocyte proteins. Their major role is initiating inflammation by releasing inflammatory cytokines in response to tissue damage or infection.
ILCs develop from the same common lymphoid precursor as T and B lymphocytes, however they lack the recombination activating genes (RAGs) that allow T and B lymphocytes to be antigen-specific. There are two main types of ILCs: cytotoxic and noncytotoxic.
Cytotoxic ILCs
Cytotoxic ILCs are better known as natural killer cells (NK cells), and have a role in eliminating cells stressed by viral infection or neoplasia. These cells contain granules with perforin and granzyme, which allows them to destroy target cells. After identifying a target cell, the NK cell releases perforin, which forms holes in the target cell, allowing granzyme to enter and lyse cellular components. NK cells are distinguished from other lymphocytes by their expression of CD16 and CD56. They also express CD2, a receptor for a subunit of IL-2.
NK cells use two types of activating receptors to identify target cells: immunoglobulin-like receptors and C-type lectin-like receptors. These receptors bind to proteins expressed by cells undergoing stress. NK cells also have inhibitory receptors, which bind to proteins expressed on class I MHC. Because all nucleated cells express MHC, these inhibitory receptors prevent the NK cell from destroying normal cells. However, cellular stress often results in decreased class I MHC expression, so these inhibitory receptors do not receive a signal. When combined with increased expression of proteins that bind to activating receptors, this “integration” of signals allows for activation of the NK cell. Neat!
NK cells also produce interferon-ɣ, which activates macrophages against intracellular pathogens. This particular role is discussed further in the Adaptive Immunity section.
Noncytotoxic ILCs
Noncytoxic ILCs follow a somewhat similar subtyping pathway as T helper cells (discussed in Adaptive Immunity), which is useful for helping you remember what they do! Each subtype has a transcriptional regulator gene, and produces a set of cytokines when that cell is activated. The types of noncytotoxic ILCs are summarized below:
| ILC | Transcriptional Regulator | Cytokines Produced | Function |
|---|---|---|---|
| Group 1 ILCs | T-bet | IFN-ɣ TNF | Defense against intracellular bacteria and parasites (similar to Th1 cells) |
| Group 2 ILCs | GATA-3 | IL-4 IL-5 IL-13 | Allergic and parasitic response (similar to Th2 cells) |
| Group 3 ILCs | RORɣt | IL-17 IL-22 | Development of lymphoid tissue Responses against extracellular bacteria (similar to Th17 cells) |
A brief note on natural killer cells:
Natural killer cells are actually considered part of the group 1 ILC family.
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Murphy KP, Janeway CA, Travers P et al. Janeway’s Immunobiology, Eighth Edition.
