Innate lymphoid cells are pivotal actors in allergic, inflammatory and autoimmune diseases

Abstract

Innate lymphoid cells (ILCs) are lymphoid cells that do not express V(D)J-rearranged receptors and play a role in the innate immune system. ILCs are categorized into three groups with respect to their function in the immune system. ILC1 induces production of IFN-γ via T-box expressed on T cells, ILC2 promotes production of type 2 cytokines via GATA-binding protein-3 and ILC3 promotes IL-17 and IL-22 production via retinoic acid receptor-related orphan receptor-γt. ILCs can maintain homeostasis in epithelial surfaces by responding to locally produced cytokines or direct recognition of danger patterns. Altered epithelial barrier function seems to be a key point in inappropriate activation of ILCs to promote inflammatory and allergic responses. ILCs play an essential role in initiation and maintenance of defense against infections as well as immune-mediated diseases. In this paper, we discuss the role of ILCs in inflammatory, allergic and autoimmune diseases.

Keywords:

• disease
• immunity
• innate lymphoid cells

Financial & competing interest’s disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Innate lymphoid cells (ILCs) encompass a newly discovered family of innate immune system with three main subgroups.

• ILC1s mainly produce IFN-γ and exert cytotoxic effects comparable to Th1 cell and cytotoxic T cell functions from adaptive immune system.

• ILC2s promote expansion and differentiation of Th2 cells and promote allergic airway inflammation, chronic rhinosinusitis and atopic dermatitis if inappropriately activated.

• ILC3s play a role in innate immune system similar to Th17 cells from adaptive immune system and induce production of IL-17.

• Recent studies show that ILCs regulate associated adaptive immune responses by both production of cytokines and presentation of antigens via MHCII.

• ILC1s and ILC3s are attributed to the pathogenesis of inflammatory bowel diseases and psoriasis, while ILC2s have been recognized as pivotal actors in the scenario of allergic diseases, asthma, atopic dermatitis and also chronic rhinosinusitis.

• Altered epithelial barrier function and subsequent inappropriate exposure of resident ILCs to environmental antigens seem to be a key point in initiation of inflammatory and allergic responses whether in the intestine, airways and lungs or skin.

• Theoretically, targeting of the ILCs may be of value to treat immune-mediated diseases but it is not possible yet as they are involved in many vital functions of the body such as tissue repair and homeostasis. It should be kept until expansion of our knowledge about characteristics, functions and distribution of ILCs and their exact role in each disease.

Notes