Th17 cells: critical mediators of host responses to burn injury and sepsis

Abstract

Th cells have long been recognized as vital components of the adaptive immune system. Until recently, CD3(+)CD4(+) Th cells were divided into cell-mediated Th1 or humoral Th2 responses. However, the Th1-Th2 hypothesis failed to accommodate the more recently described Th17 cells. Today, the major Th cell subsets include Th1, Th2, Th9, Th17, Th22, and Tregs, each of which produce specific effector cytokines under unique transcriptional regulation. Specifically, Th17 cells produce effector cytokines IL-17, IL-21, and IL-22 under the regulation of ROR-γt. Th17 lymphocytes were first described as orchestrators of neutrophil recruitment and activation and as key players in chronic inflammation and autoimmunity. More recent evidence suggest that Th17 lymphocytes and their effector cytokines play a crucial role in maintaining mucosal immunity and barrier integrity, including the skin, lung, and gut. Burn injury induces global changes to the systemic immune response, including suppressed immune function and increased susceptibility to infection. Moreover, burn trauma is associated with remote organ injury. This relationship between burn and remote organ injury supports the hypothesis that immune suppression may facilitate the development of sepsis, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome in critically ill burn patients. Herein, we discuss this emerging adaptive cell subset in critical care settings, including burn injury and clinical sepsis, and highlight the potential therapeutic role of IL-22.

Neutrophil migration in infection and wound repair: going forward in reverse

“…In several models, T cells and T cell-produced cytokines are important for neutrophil recruitment to infection, including Streptococcus pneumonia 81 and Helicobacter pylori 82 infections. Many factors contribute to the crosstalk between T cells and neutrophils in the context of infection 83 , but the involvement of the cytokine IL-17 seems to be particularly important 84,85 . In a cutaneous model of S. aureus infection, resistance to infection depends on the presence of neutrophils 86 , and both αβ T cells and IL-17-producing T cells have been shown to be important for the neutrophil response 74 .…”

Burn Wound γδ T-Cells Support a Th2 and Th17 Immune Response

“…10,11 Th17 cells also play a critical role in maintaining barrier integrity of the skin, lung and gut. 12 …”

The Role of Aryl Hydrocarbon Receptor in Interleukin-23-Dependent Restoration of Interleukin-22 Following Ethanol Exposure and Burn Injury

“…19 The stimulation of TCR induces a series of intracellular signaling cascade that includes the activation of protein kinases and the release of intracellular calcium ions. 20,21 We have shown that the decrease in T cell IFN- γ may result from alterations in T cell intracellular signaling cascade including alterations in mitogen activated protein kinases.…”