Innate Lymphoid Cells in Crohn's Disease

Abstract

Innate lymphoid cells (ILCs) are a large family of cells of the immune system that performs various functions in immune defense, inflammation, and tissue remodeling. As a part of the innate immune system, ILCs are a distinct form of lymphocytes different from T and B cells. ILCs can provide host defense against the source of infection and initiate the repair and remodeling processes to restore and maintain host body homeostasis. The number of patients with Crohn's disease (CD) worldwide has continued to increase in recent years and this disease has brought sickness and death to many families. Numerous studies have found that ILCs also undergo a series of alternations during the development of CD and contribute to this disease. Despite this, the pathogenesis of CD is still not fully explained. So, we keep researching and exploring. In this review, we have closely linked the latest progress on ILCs and CD, and introduced, in detail, the specific roles of four different types of ILCs in CD. We also describe new progress in the pathogenesis of CD, with particular emphasis on the plasticity of ILC3s in this disease. These new studies and findings may provide new insights and breakthrough points for the treatment of CD.

Keywords: Crohn’s disease; inflamma; innate immune system; innate lymphoid cells; mucosal homeostasis.

Figure 1

The role of different subgroups of innate lymphoid cells (ILCs) in the intestine. Different ILC subgroups secrete different characteristic cytokines that participate in intestinal immunity and maintain homeostasis. Changes in the ILC subtype ratio and subsequent secretion imbalances in the intestine can cause intestinal diseases.

Figure 2

Causes of Crohn’s disease (CD). Genetic susceptibility is one of the important causes of CD patients. Disturbances of the microflora and environmental factors can cause abnormal immune responses, including innate and adaptive immunity, leading to intestinal inflammation. Disease outbreaks are related to environmental factors such as antibiotic use, stress and smoking. ILCs are activated by cytokines and cell surface-bound molecules to produce distinct sets of cytokines with important consequences for tissue homeostasis and disease. ILCs display a high degree of plasticity and can trans-differentiate depending on the inflammatory environment (TL1A, TNF-like ligand 1A).

Figure 3

The plasticity of innate lymphoid cells (ILCs) contributes to Crohn’s disease (CD). In a healthy state, NCR⁺type3 ILC form the majority of ILCs in the lamina propria of the intestine. IL-22 is then produced, which is important for tissue regeneration and the secretion of mucous, antimicrobial peptides (AMPs) and IL-10. In the inflamed intestine of CD patients, the majority of ILCs has a type1 ILC phenotype and produce IFN-γ and TNF. The plasticity of type 2 ILCs and type 3 ILCs, allowing trans-differentiation into type 1 ILCs involved in the pathogenesis of intestinal inflammatory diseases such as CD. Under the influence of IL-12 and IL-2 regulated by DCs, the differentiation of type 3 ILCs to type 1 ILCs increases. In addition, under the action of IL-12, type 2 ILCs can also be converted into type 1 ILCs. Type 1 ILCs, before and after transformation, jointly promoted the increase of interferon (IFN)-γ production. This transformation is reversible, and type 1 ILCs can revert to type 3 ILCs in the presence of IL-23, IL-1β, and retinoic acid (RA) secreted by DCs.