T h17 cells develop in response to extracellular bacterial and fungal infections and induce inflammatory reactions that destroy these organisms (Fig. 1). The major cytokines produced by Th17 cells are IL-17 and IL-22. This T cell subset was discovered during studies of inflammatory diseases, many years after Th1 and Th2 sub sets were described, and its role in host defense was established later.

Fig1. Functions of Th17 cells. Th17 cells produce the cytokine interleukin-17 (IL-17), which induces production of chemokines and other cytokines from various cells, and these recruit neutrophils (and monocytes, not shown) into the site of inflammation. Some of the cytokines made by Th17 cells, notably IL-22, function to maintain epithelial barrier function in the intestinal tract and other tissues. APC, Antigen-presenting cell; CSFs, colony-stimulating factors; TNF, tumor necrosis factor.

The major function of Th17 cells is to stimulate the recruitment of neutrophils and, to less extent, monocytes, thus inducing the inflammation that accompanies many T cell–mediated adaptive immune responses. Recall that inflammation also is one of the principal reactions of innate immunity. Typically, when T cells stimulate inflammation, the reaction is stronger and more prolonged than when it is elicited by innate immune responses only. IL-17 secreted by Th17 cells stimulates the production of chemokines from other cells, and these chemokines are responsible for leukocyte recruitment. Th17 cells also stimulate the production of antimicrobial substances, called defensins, that function like locally produced endogenous antibiotics. IL-22 produced by Th17 cells induces epithelial cell defensin production, helps to maintain the integrity of epithelial barriers and may promote repair of damaged epithelia.

These reactions of Th17 cells are critical for defense against fungal and bacterial infections, especially in epithelial barrier tissues. These microbes can survive outside cells but are rapidly destroyed once they are phagocytosed, especially by neutrophils. Rare individuals who have inherited defects in Th17 responses are prone to developing chronic mucocutaneous candidiasis and bacterial abscesses in the skin. Th17 cells are also implicated in numerous inflammatory diseases, and antagonists of IL-17 and of the Th17-inducing cytokine IL-23 are very effective treatments for psoriasis, an inflammatory skin disease. An antagonist that neutralizes IL-12 and IL-23 (by binding to a protein shared by these two-chain cytokines), and thus inhibits the development of both Th1 and Th17 cells, is used for the treatment of inflammatory bowel disease and psoriasis.

Development of Th17 Cells

 The development of Th17 cells from naive CD4+ cells is driven by cytokines secreted by dendritic cells (and macrophages) in response to fungi and extracellular bacteria (Fig.2). Recognition of fungal glycans and bacterial peptidoglycans and lipopeptides by innate immune receptors on dendritic cells stimulates the secretion of several innate proinflammatory cytokines, including IL-1, IL-6, and IL-23. IL-6 and IL-23 activate the transcription factor Stat3. Signals induced by these innate inflammatory cytokines and another cytokine called transforming growth factor β (TGF-β), in com bination with TCR signals, induce the expression of the transcription factor RORγT. These transcription fac tors are required for Th17 differentiation. Interestingly, TGF-β is a powerful inhibitor of immune responses, but when present together with IL-6 or IL-1, it promotes the development of Th17 cells. 

Fig 2. Dendritic cells and other immune cells that respond to different types of microbes secrete cytokines that induce the development of antigen-activated CD4+ T cells into Th17

مواضيع ذات صلة

Th2 Cells

Th1 Cells

Subsets of CD4+ Helper T Cells Distinguished by Cytokine Profiles

Decline of the Immune Response

Migration of T Lymphocytes in Cell- Mediated Immune Reactions

Functional Responses of T Lymphocytes to Antigen and costimulation

الخلايا القاتلة غير المتخصصة

البلعمة

المناعة المتأصلة (غير المتخصصة)

Biochemical Pathways of T Cell Activation

Stimuli for Activation of CD8+ T Cells

Type I Hypersensitivity Reactions