Group 3 innate lymphoid cells (ILC3) actively participate in mucosal defense and homeostasis through prompt secretion of IL-17A, IL-22, and IFN-γ. Reports identify two ILC3 lineages: a CCR6⁺T-bet⁻ subset that appears early in embryonic development and promotes lymphoid organogenesis and a CCR6⁻T-bet⁺ subset that emerges after microbial colonization and harbors NKp46⁺ ILC3. We demonstrate that NKp46 expression in the ILC3 subset is highly unstable. Cell fate mapping using Ncr1^CreGFP × Rosa26^RFP mice revealed the existence of an intestinal RFP⁺ ILC3 subset (Ncr1^FM) lacking NKp46 expression at the transcript and protein levels. Ncr1^FM ILC3 produced more IL-22 and were distinguishable from NKp46⁺ ILC3 by differential CD117, CD49a, DNAX accessory molecule-1, and, surprisingly, CCR6 expression. Ncr1^FM ILC3 emerged after birth and persisted in adult mice following broad-spectrum antibiotic treatment. These results identify an unexpected phenotypic instability within NKp46⁺ ILC3 that suggests a major role for environmental signals in tuning ILC3 functional plasticity.

Innate lymphoid cells (ILCs) are a group of innate immune cells that possess overlapping features with T cells, although they lack antigen-specific receptors. ILCs consist of five subsets-ILC1, ILC2, ILC3, lymphoid tissue inducer (LTi-like) cells, and natural killer (NK) cells. They have significant functions in mediating various immune responses, protecting mucosal barrier integrity and maintaining tissue homeostasis in the lung, skin, intestines, and liver. ILCs react immediately to signals from internal and external sources. Emerging evidence has revealed that dietary micronutrients, such as various vitamins and minerals can significantly modulate immune responses through ILCs and subsequently affect human health. It has been demonstrated that micronutrients control the development and proliferation of different types of ILCs. They are also potent immunoregulators in several autoimmune diseases and play vital roles in resolving local inflammation. Here, we summarize the interplay between several essential micronutrients and ILCs to maintain epithelial barrier functions in various mucosal tissues and discuss their limitations and potentials for promoting human health.

Innate lymphoid cells (ILCs) are a recently discovered type of innate immune lymphocyte. They include three different groups classified by the nature of the transcription factors required for their development and by the cytokines they produce. ILCs mainly reside in tissues close to the mucosal barrier such as the respiratory and gastrointestinal tracts. Due to their close proximity to the mucosal surface, ILCs are exposed to a variety of both commensal and pathogenic bacteria. Under non-pathological conditions, ILCs have been shown to be important regulators for the maintenance of tissue homeostasis by mutual interactions with the microbiome. Besides these important functions at homeostasis, several studies have also provided emerging evidence that ILCs contribute to defense against pathogenic bacterial infection by responding rapidly to the pathogens as well as orchestrating other immune cells. In this review, we summarize recent advances in our understanding of the interactions of ILCs and bacteria, with special focus on the function of the different ILC subsets in bacterial infections.

Septic shock/severe sepsis is a deregulated host immune system response to infection that leads to life-threatening organ dysfunction. Lung inflammation as a form of acute lung injury (ALI) is often induced in septic shock. Whereas macrophages and neutrophils have been implicated as the principal immune cells regulating lung inflammation, group two innate lymphoid cells (ILC2s) have recently been identified as a new player regulating immune homeostasis. ILC2 is one of the three major ILC subsets (ILC1s, ILC2s, and ILC3s) comprised of newly identified innate immune cells. These cells are characterized by their ability to rapidly produce type 2 cytokines. ILC2s are predominant resident ILCs and, thereby, have the ability to respond to signals from damaged tissues. ILC2s regulate the immune response, and ILC2-derived type 2 cytokines may exert protective roles against sepsis-induced lung injury. This focused review not only provides readers with new insights into the signaling mechanisms by which ILC2s modulate sepsis-induced lung inflammation, but also proposes ILC2 as a novel therapeutic target for sepsis-induced ALI.

Innate lymphoid cells (ILCs) are a newly identified subset of innate cells that play fundamentally crucial roles for early immune defense at mucosal and non-mucosal sites. ILCs consist of ILC1s, ILC2s and ILC3s, which each have distinct transcription factors controlling their development and function. Interestingly, each of the ILC subsets represents the innate counterparts of CD4 + helper T-cell subsets T h1 , T h2 and T h17 on the basis of transcriptional regulation. ILC1s that produce IFN-γ or TNF-α, ILC2s that produce T h2 -type cytokines mainly such as IL-5 or IL-13 and ILC3s have been recently reported and reviewed in terms of IL-22- or IL-17-producing function and cell development. However, in this relatively new field, it remains likely that additional functional and regulatory mechanisms remain to be explored. More recent findings show that ILC3s are regulated by RORγt, which plays an important role for the mucosal barrier and surface protection against pathogenic bacterial infection. ILC3s might cooperate with other cells (e.g. T cells or dendritic cells) directly or indirectly, and subsequently ILC3s have impact on tissues with prompt regulation. Especially, ILC3s in mucosal site are well known to protect the intestinal surface barrier through inducible anti-microbial peptides via IL-22. Here, I will summarize and discuss the roles, function and heterogeneity of ILC3s in mucosal tissues.