Lung-resident γδ T cells and their roles in lung diseases

Abstract

γδ T cells are greatly enriched in mucosal and epithelial sites, such as the skin, respiratory, digestive and reproductive tracts, and they are defined as tissue-resident immune cells. In these tissues, the characteristics and biological roles of γδ T cells are distinguished from each other. The lungs represent the most challenging immunological dilemma for the host, and they have their own effective immune system. The abundance of γδ T cells, an estimated 8-20% of resident pulmonary lymphocytes in the lung, maintains lung tissue homeostasis. In this review, we summarize the recent research progress regarding lung-resident γδ T cells, including their development, residency and immune characteristics, and discuss the involvement of γδ T cells in infectious diseases of the lung, including bacterial, viral and fungal infections; lung allergic disease; lung inflammation and fibrosis; and lung cancer.

Keywords: cancer; infection; inflammation; lung; tissue-resident; γδ T cells.

Figure 1

The roles of lung resident γδT cells in bacterial and viral infections. Lung resident γδ T cells can be activated by antigens, pathogen‐associated molecular patterns (PAMPs), damage‐associated molecular patterns (DAMPs), activating receptor ligands or cytokine signalling, and they are involved in lung infection diseases. (a) During bacterial infection, activated lung γδ T cells produce interleukin‐17 (IL‐17), which recruits neutrophils, induces mature granuloma formation or induces T helper type 17 (Th17) immune responses to perform their defence functions. Moreover, activated lung γδ T cells can produce interferon‐γ (IFN‐γ) to activate pulmonary dendritic cells (DCs) and alveolar macrophages. Additionally, lung γδ T cells induce memory immune response. (b) During viral infections, activated lung γδ T cells produce several types of cytokines, among which some inhibit virus replication and some induce or inhibit lung inflammation.

Figure 2

The roles of lung resident γδ T cells in allergic disease. (a) Lung resident γδ T cells promote allergic inflammation. By producing interleukin‐4 (IL‐4), lung γδ T cells enhance specific IgE production, T helper type 2 (Th2) responses and eosinophil influx. Additionally, by producing interferon‐γ (IFN‐γ), lung γδ T cells inhibit IL‐10‐producing CD4⁺ CD25⁺ regulatory T cell functions. (b) Lung‐resident γδ T cells suppress allergic inflammation. By producing IL‐17A, lung γδ T cells inhibit Th2‐driven inflammation and eosinophil influx. Antigen‐specific regulatory γδ T cells inhibit specific IgE production. During this process, ILC2 cells might inhibit γδ T‐cell activation to control airway hyperresponsiveness.