Precarious Balance: Th17 Cells in Host Defense

Department of Pediatrics, Division of Immunology and Transplantation Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Infection and immunity (Impact Factor: 3.73). 11/2009; 78(1):32-8. DOI: 10.1128/IAI.00929-09
Source: PubMed


Lineage-specific responses from the effector T-cell repertoire form a critical component of adaptive immunity. The recent identification of Th17 cells-a third, distinct lineage of helper T cells-collapses the long-accepted paradigm in which Th1 and Th2 cells distinctly mediate cellular and humoral immunity, respectively. In this minireview, we discuss the involvement of the Th17 lineage during infection by extracellular bacteria, intracellular bacteria, and fungi. Emerging trends suggest that the Th17 population bridges innate and adaptive immunity to produce a robust antimicrobial inflammatory response. However, because Th17 cells mediate both host defense and pathological inflammation, elucidation of mechanisms that attenuate but do not completely abolish the Th17 response may have powerful implications for therapy.

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Available from: Elizabeth Mellins, Dec 17, 2013
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    • "Because of the discovery of an IL-17-producing T-cell subset, known as Th17, numerous studies have revealed IL-17 as a pro-inflammatory cytokine involved in the pathogenesis of autoimmune disorders as well as in response to certain pathogens at both the barrier site and at a systemic level (O'Connor et al., 2010; Miossec and Kolls, 2012). Th17 cells have a role in the protection against extracellular bacteria and fungi (Zhu and Paul, 2008; Zhu et al., 2010), particularly those colonizing the respiratory and gastrointestinal tracts and the skin (Peck and Mellins, 2010). The protective effects of IL-17-producing cells have been demonstrated in patients with hyper-immunoglobulin E syndrome, who suffer from recurrent infections with Candida albicans (C. "
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    ABSTRACT: Propionibacterium acnes is a Gram-positive commensal bacterium thought to be involved in the pathogenesis of acne vulgaris. While the ability of P. acnes in the initiation of pro-inflammatory responses is well documented, little is known about adaptive immune responses to this bacterium. The observation that infiltrating immune cells consist mainly of CD4(+) T cells in the perifollicular space of early acne lesions suggests that helper T cells may be involved in immune responses caused by the intra-follicular colonization of P. acnes. A recent report showing that P. acnes can induce IL-17 production by T cells suggests that acne might be a Th17-mediated disease. In line with this, we show in this work that, in addition to IL-17 A both Th1 and Th17 effector cytokines, transcription factors and chemokine receptors are strongly upregulated in acne lesions. Furthermore, we found that, in addition to Th17, P. acnes can promote mixed Th17/Th1 responses by inducing the concomitant secretion of IL-17 A and IFNγ from specific CD4(+) T cells in vitro. Finally, we show that both P. acnes-specific Th17 and Th17/Th1 cells can be found in the peripheral blood of patients suffering from acne and, at lower frequencies, in healthy individuals. We therefore identified P. acnes-responding Th17/Th1 cells as previously unreported CD4(+) sub-population involved in inflammatory acne.Journal of Investigative Dermatology accepted article preview online, 10 July 2014; doi:10.1038/jid.2014.290.
    Journal of Investigative Dermatology 07/2014; DOI:10.1038/jid.2014.290 · 7.22 Impact Factor
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    • "By contrast, the roles of adaptive immune cells in the generation of protective anti-cryptococcal infection immune responses have been widely accepted. Studies have shown that increased IL-17A production, a pro-inflammatory cytokine which is predominantly secreted by CD4+ T cells, is associated with cryptococcal burden (5,7). Furthermore, IL-17A secreted by CD4+ T helper (Th)17 cells is involved in multiple roles as a ‘bridge’ that is associated with innate and adaptive immune responses. "
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    ABSTRACT: Cryptococcosis is a potentially fatal fungal disease commonly identified in patients with acquired immunodeficiency syndrome. Cryptococcus infection induces strong pro-inflammatory cytokine secretion, i.e. type-I interferon (IFN-I) via the Toll-like receptor signaling pathway. However, innate immune responses are insufficient in host defense against fungi infection and the clearance of Cryptococcus is dependent on the T helper (Th)17 cell-mediated mucosal immune response. In this study, IFN-I was identified as the early response cytokine to Cryptococcus neoformans infection via quantitative PCR (qPCR) and IFN-I was demonstrated to be crucial for interleukin (IL)-17A secretion in T cells, but not in innate immune cells. In addition, blockade of IFN-I reduced the protein expression levels of IL-22 and IL-23 in Th17 cells in vitro. These results suggest additional functions of IFN-I in immune regulation, which may be pivotal for the development of clinical immune therapy.
    Experimental and therapeutic medicine 04/2014; 7(4):869-872. DOI:10.3892/etm.2014.1517 · 1.27 Impact Factor
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    • "CD4+ T lymphocytes expressing interleukin (IL)-17 (Th17 cells) constitute a distinct subset of effector T cells with a specific transcriptional program, defined by the lineage determining factors RORγt and RORα[1], [2]. Despite their crucial contribution to protection against extracellular pathogens [3], Th17 cells have been implicated in the immunopathology of a range of inflammatory diseases such as psoriasis [4], rheumatoid arthritis [5] and multiple sclerosis [6], [7]. "
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    ABSTRACT: The aryl hydrocarbon receptor (AhR) has been attributed with anti-inflammatory effects in the development of pathological immune responses leading to experimental autoimmune encephalomyelitis (EAE) via the induction of regulatory T cells. In agreement with previously published findings, we find that TCDD administration confers protection from EAE, however, this immuno-modulatory effect was not the consequence of de novo Treg generation, but the inhibition of Th17 cell differentiation. Systemic application of FICZ at the time of immunization also reduced EAE pathology albeit to a lesser degree than TCDD. In vitro Th17 differentiation in the presence of AhR agonists, including TCDD, promoted IL-17 and IL-22 expression, but did not induce Treg differentiation. AhR affinity influenced the amounts of IL-17 and IL-22 protein that was secreted by Th17 cells, but did not seem to affect susceptibility to EAE in vivo. Making use of conditional AhR-deficient mice, we show that the anti-inflammatory effect of TCDD depends on AhR activation in both T cells and dendritic cells, further emphasising the ability of TCDD to interfere with T effector cell differentiation in vivo. The dichotomy between the in vivo and in vitro effects of AhR reveals the complexity of the AhR pathway, which has the capacity of affecting different AhR-expressing cell types involved in mounting immune responses, thus participating in defining their outcome.
    PLoS ONE 11/2013; 8(11):e79819. DOI:10.1371/journal.pone.0079819 · 3.23 Impact Factor
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