A tale of two cytokines: IL-17 and IL-22 in asthma and infection

Abstract

The Th17 pathway has recently been shown to play a critical role in host defense, allergic responses and autoimmune inflammation. Th17 cells predominantly produce IL-17 and IL-22, which are two cytokines with broad effects in the lung and other tissues. This review summarizes not only what is currently known about the molecular regulation of this pathway and Th17-related cytokine signaling, but also the roles of these cytokines in pathogen immunity and asthma. In the last 5 years, the Th17 field has rapidly grown and research has revealed that the Th17 pathway is essential in lung pathogenesis in response to exogenous stimuli. As work in the field continues, it is expected that many exciting therapeutic advances will be made for a broad range of diseases.

Keywords::

• allergy
• cytokines
• lung
• pneumonia
• T cells

Financial & competing interests disclosure

This work was supported by a Research Advisory Committee Fellowship from Children’s Hospital of Pittsburgh of UPMC (ML Manni), NIH T32 HL007563 (KR Robinson) and NIH NHLBI 1R01HL107380 (JF Alcorn). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The Th17 lineage of T cells was first described in 2006 and is characterized by expression of retinoic acid-related orphan receptor α (RORα), retinoic acid-related orphan receptor γ thymus (RORγT) and STAT3.

• Several cytokines, such as IL-6, IL-1β, TGF-β, IL-21 and IL-23 positively regulate Th17 polarization and function.

• Th17 cells are opposed by the functions of Type 1 and 2 interferons, IL-27 and IL-4.

• Segmented filamentous bacteria in the gut microbiome regulate Th17 (and T_reg) priming and likely impact lung immunity.

• Th17 cells (and several additional lymphocytes) secrete IL-17 and IL-22 as effector cytokines.

• IL-17 primarily enhances inflammation by inducing chemokine and growth factor production by the lung epithelium. IL-17 and IL-22 stimulate antimicrobial peptide production and IL-22 regulates epithelial repair.

• IL-17, IL-22 and IL-23 all play emerging roles in asthma and allergy which may be both beneficial and detrimental depending on context.

• In host defense, IL-17, IL-22 and IL-23 promote pathogen clearance, drive inflammation and orchestrate epithelial repair.

Notes