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

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.