T Cell Extracellular Traps: Tipping the Balance Between Skin Health and Disease

Abstract

The role of extracellular traps (ETs) in the innate immune response against pathogens is well established. ETs were first identified in neutrophils and have since been identified in several other immune cells. Although the mechanistic details are not yet fully understood, recent reports have described antigen-specific T cells producing T cell extracellular traps (TETs). Depending on their location within the cutaneous environment, TETs may be beneficial to the host by their ability to limit the spread of pathogens and provide protection against damage to body tissues, and promote early wound healing and degradation of inflammatory mediators, leading to the resolution of inflammatory responses within the skin. However, ETs have also been associated with worse disease outcomes. Here, we consider host-microbe ET interactions by highlighting how cutaneous T cell-derived ETs aid in orchestrating host immune responses against Cutibacterium acnes (C. acnes), a commensal skin bacterium that contributes to skin health, but is also associated with acne vulgaris and surgical infections following joint-replacement procedures. Insights on the role of the skin microbes in regulating T cell ET formation have broad implications not only in novel probiotic design for acne treatment, but also in the treatment for other chronic inflammatory skin disorders and autoimmune diseases.

Extracellular traps are evident in Romanowsky‐stained smears of bronchoalveolar lavage from children with non‐cystic fibrosis bronchiectasis

“…LETs have been considered in acne 39 and autoimmune diseases 40 but we are unaware of any reports describing LETs involvement in respiratory conditions. There is some evidence from in vitro studies that LETs may be generated in response to infectious stimuli, 41 whereas other reports suggest LET‐associated inflammation may disrupt wound healing and promote tissue damage 39 . Follow‐up testing with lymphocyte‐specific staining methods is needed to confirm the presence of LETs in BAL and sputum and to elucidate the lymphocyte cell types that may be generating these ETs 40 …”

Research progress on the neutrophil components and their interactions with immune cells in the development of psoriasis

“…63 Compared to healthy controls, patients with psoriasis have higher levels of NETs in their skin lesions and peripheral blood. 63 Indicating that NETs play an important role in psoriasis.…”

“…Indicating that NETs not only have anti‐infective effects but also play a role in autoimmunity. Eosinophils, mast cells, neutrophils, macrophages, and Th17 cells can all produce extracellular traps 63 . Compared to healthy controls, patients with psoriasis have higher levels of NETs in their skin lesions and peripheral blood 63 .…”

“…Eosinophils, mast cells, neutrophils, macrophages, and Th17 cells can all produce extracellular traps 63 . Compared to healthy controls, patients with psoriasis have higher levels of NETs in their skin lesions and peripheral blood 63 . Indicating that NETs play an important role in psoriasis.…”

T-Cell Mediated Immunity in Merkel Cell Carcinoma

“…Extracellular trap (ET) formation is not unique to neutrophils as ETs have been described in other immune cells [ 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 ]. The work from our lab and others has shown that antigen-specific T-cells can release T-cell ETs that trap and kill microbes [ 128 , 138 ]. These observations suggest a role for ETs in immunity.…”