Role of Mast Cells and Type 2 Innate Lymphoid (ILC2) Cells in Lung Transplantation

Figure 2

Interactions of mast cells (MC) and type 2 innate lymphoid cells (ILC2) in lung rejection after transplantation. After lung transplantation, damaged airway ECs release mediators such as IL-25, IL-33, and TSLP which caused activation of MCs and ILC2s and the subsequent release of IL-4, IL-5, and IL-13. IL-4 and IL-13 also enhance Th2 cell maturation and activation and stimulate DCs which interact with ECs to enhance the release of IL-33. MCs also produce IL-33 upon activation. The effect of IL-33 on ILC2-mediated release of IL-13 is enhanced by ATP produced by damaged ECs. LTD4 and PGD2 released by activated MCs further recruits and activates ILC2s to produce IL-2, −4, −5, −9, and −13. IL-13 released by Th2 cells plays a dual role in the induction of organ rejection and in promoting tolerance. Moreover, IL-13 can induce epithelial cell hyperproliferation and collagen deposition leading to pulmonary fibrosis. IL-4 released by MC also triggers fibroblast activation leading to lung fibrosis. MC-derived TGF-β1 further enhances fibrotic activity. Abbreviations: Areg: amphiregulin; DCs: dendritic cells; ECs: epithelial cell; IL: interleukin; LTD4: leukotriene D4; PGD2: prostaglandin D2; TGF-β1: transforming growth factor beta; Th2: T helper type 2 cell; TSLP: thymic stromal lymphopoietin.