Directing traffic: IL‐17 and IL‐22 coordinate pulmonary immune defense

Abstract

Summary Respiratory infections and diseases are among the leading causes of death worldwide, and effective treatments likely require manipulating the inflammatory response to pathogenic microbes or allergens. Here we review mechanisms controlling the production and functions of interleukin-17 (IL-17) and IL-22, cytokines that direct several aspects of lung immunity. Innate lymphocytes (γδT cells, natural killer cells, innate lymphoid cells) are the major source of IL-17 and IL-22 during acute infections, while CD4+ T-helper 17 (Th17) cells contribute to vaccine-induced immunity. The characterization of dendritic cell (DC) subsets has revealed their central roles in T-cell activation. CD11b+ DCs stimulated with bacteria or fungi secrete IL-1β and IL-23, potent inducers of IL-17 and IL-22. On the other hand, recognition of viruses by plasmacytoid DCs inhibits IL-1β and IL-23 release, increasing susceptibility to bacterial superinfections. IL-17 and IL-22 primarily act on the lung epithelium, inducing antimicrobial proteins and neutrophil chemoattractants. Recent studies found that stimulation of macrophages and DCs with IL-17 also contributes to anti-bacterial immunity, while IL-22 promotes epithelial proliferation and repair following injury. Chronic diseases such as asthma and chronic obstructive pulmonary disease have been associated with IL-17 and IL-22 responses directed against innocuous antigens. Future studies will evaluate the therapeutic efficacy of targeting the IL-17/IL-22 pathway in pulmonary inflammation.

Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses

“…The role of Th17 in protection against viral infections is not clear: while some studies demonstrated their role in protection (32,33), others suggested no role (34) or even enhancement of viral infection (35). Development of Th17 cells was previously associated with pulmonary immune defense (36) or inflammation in chronic obstructive pulmonary disease and lung cancer (37). Modest amounts of GPspecific + or CD103 -CD8 + T cells were capable of CD107a mobilization.…”

Physiology and immunology of mucosal barriers in catfish (Ictalurus spp.)

“…In mammals, IL17 ligand expression has been linked not only to protective immunity but also excessive tissue inflammation and damage in the gut and lungs. 83 Recent work by our group identified and characterized 7 IL17 ligands and 4 IL17 receptor (IL17R) homologues from transcriptomic and genomic databases of channel catfish. To gain insight into the mucosal actions of the IL17A/Fs-associated pathway in inflammatory processes, the expression profiles of 3 IL17A/Fs and their putative receptors IL17RA and IL17RC in mucosal tissues of catfish following experimental challenge with E. ictaluri and F. columnare were investigated.…”

Intraepithelial T-Cell Cytotoxicity, Induced Bronchus-Associated Lymphoid Tissue, and Proliferation of Pneumocytes in Experimental Mouse Models of Influenza

“…The major source for IL-17 and IL-22 during acute infection is innate lymphocytes (cd T-cells and natural killer cells). However, Th17 T-cells arising from maturation of CD4 helper cells contribute to cytokine production during induced immunity (23,28,30). Il-17 is key to iBALT formation (41) with or without the participation of dendritic cells (16).…”

“…IL-17 acts by increasing expression of chemokines CXCL12 and CXCL13, which are critical for follicle formation. IL-22 promotes epithelial proliferation (18,28), including epithelial cell transformation and tumorigenesis (21), through receptors on epithelial cells involved in STAT3 activation that are not found on immune cells (48 …”