T Cells and Group 2 Innate Lymphoid Cells 2

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by local inflammation of the paranasal sinuses and nose lasting at least 12 weeks [1–3]. CRS is frequently divided into the two main phenotypes: CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The inflammatory response in CRS is well known to be controlled by CD4+ T helper cell associated cytokines including a Th1 cytokine (IFN-γ), Th2 cytokines (IL-4, IL-5, and IL-13) and Th17 cytokines (IL-17A and IL-22). Recent studies indicate that these T helper cytokines are not only produced from T cells but also from innate lymphoid cells (ILCs). Unlike T cells, ILCs lack antigen receptors but produce high levels of T helper cytokines after activation via antigen-independent stimuli including cytokines and lipid mediators. ILC can be classified into three major subsets; group 1 ILC (ILC1), ILC2, and ILC3, based on the function and production of cytokines [4, 5]. ILC1s are characterized by the production of the Th1 cytokine IFN-γ. ILC2s produce Th2 cytokines, IL-4, IL-5, and IL-13. ILC3s are characterized by the production of Th17 cytokines, IL-17A and IL-22. Currently, ILCs are viewed as an innate counterpart of T helper cells in that ILC1s, ILC2s, and ILC3s mirror Th1 cells, Th2 cells, and Th17 cells, respectively. Since both T helper cells and ILCs release the same cytokines, many groups now call IFN-γ a type 1 cytokine, IL-4, IL-5, and IL-13 type 2 cytokines and IL-17A and IL-22 type 3 (or 17) cytokines (Fig. 6.1a). Similarly, inflammation caused by these cytokines is called type 1, 2, and 3 (or 17) inflammation, respectively [4, 5, 8]. We will use the above terminology in this chapter.