Double-edged sword: γδ T cells in mucosal homeostasis and disease

Abstract

The mucosa is a tissue that covers numerous body surfaces, including the respiratory tract, digestive tract, eye, and urogenital tract. Mucosa is in direct contact with pathogens, and γδ T cells perform various roles in the tissue. γδ T cells efficiently defend the mucosa from various pathogens, such as viruses, bacteria, and fungi. In addition, γδ T cells are necessary for the maintenance of homeostasis because they select specific organisms in the microbiota and perform immunoregulatory functions. Furthermore, γδ T cells directly facilitate pregnancy by producing growth factors. However, γδ T cells can also play detrimental roles in mucosal health by amplifying inflammation, thereby worsening allergic responses. Moreover, these cells can act as major players in autoimmune diseases. Despite their robust roles in the mucosa, the application of γδ T cells in clinical practice is lacking because of factors such as gaps between mice and human cells, insufficient knowledge of the target of γδ T cells, and the small population of γδ T cells. However, γδ T cells may be attractive targets for clinical use due to their effector functions and low risk of inducing graft-versus-host disease. Therefore, robust research on γδ T cells is required to understand the crucial features of these cells and apply these knowledges to clinical practices.

Immune and Microbial Signatures Associated with PD-1 Blockade Sensitivity in a Preclinical Model for HPV+ Oropharyngeal Cancer

“…Furthermore, we included molecules such as CTLA-4 and LAG-3, which are important for optimal regulation and homeostasis of T cells within the tumor microenvironment [ 92 , 93 ]. Given our focus on oropharyngeal carcinoma, it is important to include gamma delta T cells in our future analyses since these cells defend mucosa from pathogens and maintain homeostasis for further immunoregulatory functions [ 94 ]. We recognize that it is important to expand the scope of our research for other HPV subtypes, such as HPV-35, 33, and 39, for which, at the moment, there are no preclinical murine models but are highly prevalent in minority individuals.…”

IL-27 disturbs lipid metabolism and restrains mitochondrial activity to inhibit γδ T17 cell-mediated skin inflammation

“…Frequently encountering xenobiotic invasions in these tissues, γδ T cells are poised to surveil pathogens and cellular damages and have rapid reactions to these dangers. Normally, these first lines of immune responses mediated by γδ T cells are protective to eliminate invaders or damaged cells, however, they can be pathogenic and initiate proinflammatory reactions when facing excessive or persistent stimulations, which will further endanger tissues [ 3 , 4 ]. γδ T17 (IL-17A+ γδ T) cells, for example, are located beneath the epithelial barrier, secret IL-17A when stimulated that induce chemokines and recruit neutrophils or adaptive immune cells to eliminate invasive pathogens.…”