Innate lymphoid cells and their importance in innate immune and inflammatory responses

In this article, I briefly explain the importance of innate lymphoid cells in innate immune and inflammatory responses.

Innate lymphoid cells (ILCs)

Innate immunity is generally governed by non-lymphoid cells, i.e., myeloid and epithelial cells. ILCs are a family of lymphocytes activated by infection, damage, or stress and enhancing innate and inflammatory responses. Innate lymphoid cells are devoid of the amply diverse antigen-specific receptors of B and T lymphocytes.

Innate lymphoid cells (ILCs) with cytotoxic activity – NK cells

Natural killer cells (NK cells) were the first innate lymphoid cells to be discovered. Unlike B cells and T cells, they express a fixed set of receptors, which enable the cells to be activated by indicators of infection or any damage expressed by other cells.

B cells and T cells need many days for activation to differentiate, whereas NK cells are pre-programmed for quick response to appropriate stimuli.

NK cells secrete cytokines like TNF-α and IFN-γ, which help in macrophage activation and also play an important role in early innate response to viral infections. These early innate responses control the infections till the initiation of adaptive immune responses.

NK cells express a variety of novel receptors, like activating receptors, which have specificity for various cell surface ligands as indicators of infection or other diseases.

Most of the NK activating receptors have specificity for proteins upregulated on infected or malignant cells. NK cells prohibit themselves from killing normal healthy cells by expressing inhibitory receptors.

Normal cells when infected by a virus, can not express MHC proteins and are unable to send the inhibitory signals. This leads to sending activating signals generated by the infected cell to an NK cell. This senses the cell as a target cell, and the NK cell gets activated to kill it. Thus, NK cells play an important role in our innate sensing mechanism by recognizing and eradicating the harmful cells in our body.

Some NK cells express TLRs, which may play a role in activating NK cell production of cytokines and cytotoxicity.

Innate lymphoid cells play various roles by producing cytokines

Generally, NK cells are present in lymphoid tissues and recirculate in the blood. Whereas, some innate lymphoid cells are found in mucosal tissues, such as the intestine and lungs, and the glandular tissues, such as salivary glands. In mucosal tissues and glandular tissues, they have important roles in innate immune responses.

Innate lymphoid cells can be categorized into three groups. The first group is ILC-1, which includes NK cells and ILC 1 cells, both producing IFN-γ and TNF-α, but marked cytotoxic activity is provided by NK cells.

ILC-2 cells are the second group of cells producing cytokines, such as IL-4, IL-5, IL-9, and IL-13, and give innate protection against parasitic worms. Eosinophils get activated by the cytokine IL-5 to release toxic mediators for the parasites. Whereas, IL-13 spurs contraction of smooth muscles, production of mucus, recruitment of activated macrophages, etc., which enhance expulsion of the parasitic worms.

The lymphoid tissue inducer (LTi) helps to develop secondary lymphoid organs like lymph nodes and Peyer’s patches.

Intestinal epithelial cells are induced by Interleukin-22, produced by LTi, and ILC 22 populations to produce antimicrobial peptides that help them resist bacterial infection by Salmonella typhimurium and diarrhea by rotavirus. Local inflammatory responses that give protection against fungi are promoted by some ILC3 populations.

In humans, only NK cells and ILC3s express toll-like receptors (TLRs). Epithelial cells, macrophages, and dendritic cells give rise to some factors which help induce ILCs to produce mediators. These mediators give immunity to pathogens like intracellular and extracellular viruses, bacteria, and parasites.

These locally produced factors entail cytokine IL-12, which activates ILC1S, IL-25, IL-33, and other cytokines. Prostaglandin D2 activates ILC 2S, IL-1α, and other cytokines, whereas prostaglandin E2 and leukotriene D4 activate ILC3s.

Innate immune responses activate local inflammation

Skin and other epithelial layers are the outer barriers of the innate immune system. When they get damaged, the resulting innate responses to infection or any injury can bring about a complex cascade of events known as the inflammatory response. Inflammation may be acute or chronic, depending upon the damage.

When there is a local infection or tissue damage, the sentinel cells present in the epithelial layer, e.g., macrophages, mast cells, and dendritic cells, are activated by PAMPs and DAMPs. The activation of sentinel cells causes them to phagocytose the offending invaders.

The PRR Signaling pathways also activate the antigen-presenting cells to release innate immunity mediators, which include cytokines and chemokines. In this way, triggering a series of processes collectively known as inflammatory response.


Innate lymphoid cells (ILCs) are derived from common lymphoid progenitors but do not express antigen-specific receptors. Any infection, damage, or stress activates innate lymphoid cells, a family of lymphocytes that enhance Innate and inflammatory responses.

NK cells play an important role in our innate sensing mechanism. They do it by recognizing and eradicating the harmful cells of our body. Natural killer cells (NK cells) were the first innate lymphoid cells to be discovered.

ILCs can be categorized into three groups and play various roles by producing different cytokines. Local inflammation gets activated by innate immune responses.

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