Therapeutical Measures to Control Airway Tolerance in Asthma and Lung Cancer

Abstract

Airway tolerance is a specialized immunological surveillance which is activated by the cells of the lung to deal with and distinguish between innocuous and pathogenic inhalants. However, this distinction does not always occur. Airway tolerance is necessary to avoid the development of allergic disorders, such as asthma, which is dominated by a pathological expansion of Th2 and Th17 cells in the airways. By contrast, tumor cells induce tolerogenic factors in their microenvironment to evade T-cell mediated anti-tumor-immune responses. This review updates current understandings on the effect of the cytokines TGF-β, IL-10, and IL-17A on the lung immune responses to antigen, and analyzes their involvement in allergic asthma and lung cancer. The aim of the review is to evaluate where therapeutic intervention may be feasible and where it might fail. The multifunctional role of these cytokines further complicates the decision on the timing and concentration for their use as therapeutical targets. In fact, TGF-β has suppressive activity in early tumorigenesis, but may become tumor-promoting in the later stages of the disease. This dual behavior is sometimes due to changes in the cellular target of TGF-β, and to the expansion of the induced (i)-Tregs. Similarly, IL-17A has been found to elicit pro- as well as anti-tumor properties. Thus, this pro-inflammatory cytokine induces the production of IL-6 which interferes with Treg development. Yet IL-17A could promote tumor growth in conjunction with IL-6-dependent activation of Stat3. Thus, understanding the mechanisms of airway tolerance could help to improve the therapy to both, allergic asthma and lung cancer. Hereby, asthma therapy aims to induce and maintain tolerance to inhaled allergens and therapy against lung cancer tries to inhibit the tolerogenic response surrounding the tumor.

The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma

“…Th1 mediated immune responses play a major role for tumour cell rejection. 26 Therefore, we next analyzed Th1 associated factors, expressed by CD4C T-cells in na€ ıve as well as tumour-bearing mice at different time points after lung carcinoma induction. Interestingly, we found that more than 40% of all TbetC CD4C Tcells in the lungs of tumor bearing mice co-expressed Foxp3 and CD25 ( Fig.…”

Rhinovirus inhibits IL-17A and the downstream immune responses in allergic asthma

“…Antiviral Oas1 genes are inhibited in lung CD4 þ T cells obtained from OVA-sensitized Il17a ( À / À ) mice Aeroallergen sensitization is one of the strongest risk factors for asthma. 33 However, viral infection has also been emerged as a crucial factor in the pathogenesis of this disease. 34 To understand the role of IL-17A in the regulation of different genes that are involved in the response to viral infections, we used a gene array approach in our study.…”

Serum cytokine profiles as predictors of asthma control in adults from the EGEA study

“…Additionally, this panel included two cytokines that are less often investigated in asthma [12]: Interleukin (IL)-1 receptor antagonist (IL-1Ra), an antagonist of IL-1 with antiinflammatory activity [17], and IL-10 able to inhibit pro-inflammatory cytokine synthesis [18,19].…”