Reviews and feature article
Development and function of TH17 cells in health and disease

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TH17 cells are the newest member of the TH cell family and are characterized by their ability to produce specific cytokines such as IL-17, IL-22, IL-17F, and CCL20. In this review, conditions for the differentiation of TH17 cells are defined in both murine and human systems, with discussion of TH17-specific cytokines and transcription factors. Functionally, TH17 cells contribute to host defense as a new effector TH cell subset with a role in protection against extracellular bacteria through activities on immune and nonimmune cells. Their activities, however, are also pivotal in the development of autoimmune diseases under pathologic conditions. TH17 cells are also beginning to be associated with the development and pathophysiology of allergic diseases, such as allergic contact dermatitis, atopic dermatitis, and asthma. Lymphoid tissue inducer–like cells and natural killer–like cells, termed RORγt+NKp46+ or NK-22 cells, might also play a role in allergic diseases because of their propensity to produce IL-17 and IL-22.

Section snippets

IL-17–producing CD4+ T cells: A distinct TH cell subset

The adaptive immune system is crucial for the elimination of infectious agents, but dysregulation of adaptive immune responses can also lead to the development of inflammatory and autoimmune diseases. In 1986, Mosmann et al1 proposed the TH1-TH2 paradigm of CD4+ T cell lineage commitment in which they described the presence of 2 different TH cell subsets, each expressing a distinct cytokine profile. TH1 cells develop in the presence of IL-12, a heterodimeric cytokine composed of p35 and p40

Mouse TH17 cell development

IL-23 was clearly essential for inducing IL-17–producing CD4+ T cells and autoimmunity in vivo. In vitro studies, however, revealed that it did not drive the differentiation of murine naive CD4+ T cells toward a TH17 phenotype. This observation was not completely unexpected because naive T cells do not express IL-23R. Instead, studies by Bettelli et al,15 Mangan et al,16 and Veldhoen et al17 showed that TGF-β and IL-6 together were required to induce the development of TH17 cells (Fig 1). The

TH17 cells in anti-pathogen responses and autoimmunity

Despite being involved in various autoimmune inflammatory disorders, not all TH17 effector functions are detrimental. TH17 cells play a significant role in defense of the host against certain extracellular bacteria and fungi, and emerging information suggests that this cell subset might be indirectly involved in immune protection against virus-associated pathologies as well.

TH17 cell–produced IL-17 promotes neutrophil maturation and chemotaxis, which are important in conferring protection

TH17 cells in allergic diseases

TH17 cells and their related cytokines are now beginning to show an association with allergic diseases as well. TH17 cells are highly involved in the development and maintenance of psoriasis,52 and a possible role for IL-17, IL-22, and TH17 cells in allergic contact dermatitis or atopic dermatitis (AD) is also now emerging. Nickel-specific TH0, TH1, or TH2 clones from patients with allergic contact dermatitis have been found to produce IL-17,54, 55 and allergen-specific TH17 cells have been

TCRγδ+ T cells, invariant NK T cells, NK-22 cells, and lymphoid tissue inducer–like cells: Additional subsets of IL-17– and/or IL-22–producing cells

As mentioned above, in addition to the CD4+TCRαβ+ TH17 cells that are predominantly involved in the adaptive immune response, other cell subsets, such as TCRγδ+ T cells, NK T cells, and certain NK cells, are also able to produce IL-17 in the early innate response. The rapid production of IL-17 by these cells is important for the activation and recruitment of neutrophils to sites of inflammation. It is important to note that many γδ T cells in the periphery seem to be effector memory cells that

Concluding remarks

Even though the field of murine and human TH17 cell biology has blossomed over the past few years, the role of TH17 cells in allergic diseases is just beginning to be understood. Although progress has been made, further work will need to delineate the specific functions of TH17 cells from those of other cell types that are capable of producing TH17-associated cytokines, such as IL-17 and IL-22.

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    Disclosure of potential conflict of interest: The authors are employees of Schering-Plough.

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    Copyright © 2009 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.