Skip to main content
. 2020 Feb 4;10:3111. doi: 10.3389/fimmu.2019.03111

Figure 4.

Figure 4

Innate lymphoid cells (ILCs) modulate adaptive immunity by direct or indirect interactions with other cells in the tissue. ILC2s functionally resemble Th2 cells and play a critical role in the type 2 immune response. The role of ILC2s in the establishment of an by direct interactions with Th2 cells through OX40L/OX40 under IL-33 stimulation or through indirect interactions by the section of IL-13 or amphiregulin (AREG), which then causes regulatory T cell (Treg) cell expansion and myeloid-derived suppressor cell (MDSC) activation. ILC2-derived IL-13 also stimulates dendritic cell (DC) recruitment and CCL17 production to provoke a Th2 response. ILC2s produce IL-4 to regulate Th2 differentiation, which may suggest a potential role in promoting tumor growth and metastasis. In terms of antitumor function, the release of IL-5 and IL-9 by ILC2s restrains tumor growth through eosinophils recruitment and activation and DC antigen presentation. Conversely, high expression of IL-9 is associated with T-cell transformation in humans, indicating that the anti-apoptotic properties on transformed cells promote tumorigenesis. ILC3s are important in the Th17 immune response. The direct interactions with CD4+T cells are either through MHC II/TCR or through OX40/OX40 and CD30L/CD30 to regulate T-cell survival or B-cell class switch, respectively. ILC3 migrate to the draining mesenteric lymph node to initiate an adaptive response that requires CCR7 expression. ILC3s promote IgA production in a T cell-dependent manner via the regulation of CD4+T-cell homing by sLTα3 secretion and also in a T cell-independent manner via control of B-cell homing by the release of LTα1β2. ILC3-derived IL-22 triggers epithelial serum amyloid A protein (SAA) production to induce local Th17 response in a STAT3-dependent manner. The secretion of IL-22 and GM-CSF by ILC3 stimulates macrophages and DCs to release IL-10, and this consequently results in regulatory T cell (Treg) cell expansion. In addition, IL-1β produced by macrophages activates ILC3 and leads to CD4+T-cell priming, whereas T cell-derived cytokines also cross-regulate ILC response, indicating the bidirectional interactions between ILC3 and T cell-mediated immunity.