Abstract
Innate lymphoid cells (ILCs) have emerged as a new family of immune cells with crucial functions in innate and adaptive immunity. ILC subsets mirror the cytokine and transcriptional profile of CD4+ T helper (TH) cell subsets. Hence, group 1 (ILC1), group 2 (ILC2), and group 3 (ILC3) ILCs can be distinguished by the production of TH1, TH2, and TH17-type cytokines, respectively. Cytokine release by ILCs not only shapes early innate immunity but can also orchestrate TH immune responses to microbial or allergen exposure. Recent studies have identified an unexpected effector function of ILCs as antigen presenting cells. Both ILC2s and ILC3s are able to process and present foreign antigens (Ags) via major histocompatibility complex class II, and to induce cognate CD4+ T cell responses. In addition, Ag-stimulated T cells promote ILC activation and effector functions indicating a reciprocal interaction between the adaptive and innate immune system. A fundamental puzzle in ILC function is how ILC/T cell interactions promote host protection and prevent autoimmune diseases. Furthermore, the way in which microenvironmental and inflammatory signals determine the outcome of ILC/T cell immune responses in various tissues is not yet understood. This review focuses on recent advances in understanding the mechanisms that coordinate the collaboration between ILCs and T cells under homeostatic and inflammatory conditions. We also discuss the potential roles of T cells and other immune cells to regulate ILC functions and to maintain homeostasis in mucosal tissues.
Highlights
Adaptive immune responses are tightly controlled by the selection of the T and B cell receptor repertoire and by transcriptional networks regulating commitment, expansion, and contraction of the responses
We propose the following model (Figure 1): ILC2s can be rapidly activated by various alarm signals leading to the release of TH2type cytokines, which help to induce TH2 cell responses and Dendritic cells (DCs) migration into lymph nodes (LNs) toward T cell zones
Our understanding of immune homeostasis has been challenged by the notion that environmental factors, including commensal bacteria and nutritional components, as well as cholinergic and metabolic signals can regulate immune functions and pro-inflammatory processes
Summary
Adaptive immune responses are tightly controlled by the selection of the T and B cell receptor repertoire and by transcriptional networks regulating commitment, expansion, and contraction of the responses. Group 3 ILCs include fetal lymphoid tissue-inducer (LTi) cells, as well as adult ILC3s either expressing the natural cytotoxicity receptor (NCR) NKp46 (NCR+ILC3s) or lacking this molecule (NCR−ILC3s) Cells within this group produce the TH17-type cytokines, IL-17 and/or IL-22 [9]. Additional evidence for heterogeneity among ILC subsets comes from clonal analysis in humans demonstrating that the spectrum of cytokines produced by ILC3s is diverse [18] and in some cases, both ILC2 and ILC3 cytokines are produced [19] Environmental factors, such as retinoic acid, short chain fatty acids, vitamins, aryl hydrocarbon receptor (AHR) ligands, stearyl sulfate, and probably bacterial metabolites, can shape ILC phenotypes and functions [20,21,22,23,24]. We will highlight major questions on how ILCs may cooperate with T cells thereby regulating T cell responses
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