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TH17 cells in the big picture of immunology

https://doi.org/10.1016/j.jaci.2007.06.039Get rights and content

The pathogenesis of chronic inflammatory diseases is assumed to depend on activated T cells interacting with resident tissue cells or migratory inflammatory cells. The discovery of new T-cell subsets such as the IL-17–producing TH17 and T-regulatory cells innovated our understanding of T-cell biology. Studies on new subsets confirm the important role of T cells in the instruction of tissue cells and also demonstrate the important role of feedback regulation for the polarization toward distinct T-cell subsets. The understanding of IL-17 and TH17 differentiation pathways has also changed the perspective of immunologists regarding the basis of chronic tissue inflammation, particularly where TH1 cells were considered as driving force of the pathology. This review summarizes the recent developments on TH cell subsets and integrates these findings into existing concepts of immunopathologic mechanisms.

Section snippets

T-cell functions in allergy

The understanding of T-cell responses in allergy during the last decade not only highlighted the critical importance of TH2 cells in helping B cells toward IgE expression but also revealed that TH2 cells interact with other cells such as eosinophils via IL-5; smooth muscle cells via IL-9; epithelial cells and keratinocytes via IL-13; and epithelial cells via IL-31,7 which modulate tissue processes in allergic diseases.8, 9 Particular interest has been raised regarding the transition between

TH17 cells: a separate subset

The discovery of the TH17 cells is filling an essential gap in our understanding of inflammatory processes, because it was unclear how TH1 cells actually mediate inflammation in the tissues by the expression of IFN-γ. TH17 cells are characterized by IL-17 (or IL-17A), IL-17F, IL-6, TNF-α, and IL-22 expression.32, 33, 34, 35, 36 Neutralization of IL-17, but not genetic deletion of TH1 cells, resolves tissue pathology in autoimmune models.37 Furthermore, anti–IL-17 reduces joint destruction in

TH17 cells: good or bad in allergy?

Although published data have predominantly been raised in murine systems, functions of IL-17 clearly indicate a proinflammatory role and thus identify TH17 cells as possible participants in autoimmunity. The key cytokine of TH17 cells, IL-17, is known to induce proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 as well as chemokines CXCL1, 2, and 8, which together are hallmarks of acute inflammatory processes (Table I).72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85 The chemokines

T-cell function and development revisited in the context of emerging novel subsets

A fundamental understanding of new T-cell phenotypes is that they not only interact with other lymphoid cells according to their helper function but also play an essential role in the instruction of tissue cells, which activates either nonspecific immune functions (apoptosis, mucus secretion, remodeling) or a immune-regulatory function such as the amplification of inflammation by secretion of chemokines and the induction of MHC molecules or proinflammatory cytokines. The aim of this education

Conclusion

The individual T-cell subsets orchestrate immune responses in a timely, coordinated, and tissue-adjusted manner. Accordingly, T-cell phenotypes have alternating relevance in allergic and autoimmune disease, depending on the disease progression and organ involvement. The assignment of differentiation pathways to functionally different T-cell subsets may dramatically improve treatment, because it allows therapeutic intervention before T-cell differentiation. According to human genome data, not

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    Supported by Swiss National Science Foundation grants 310000-112329, 3200B0-105865, 32600-113165, and 32000-112306; the Bonizzi-Theler Foundation Zurich; the Swiss Life Foundation Zurich; and the Global Allergy and Asthma European Network.

    Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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