Airway epithelial cells modify immune responses by inducing an anti‐inflammatory microenvironment

Abstract

The upper airways are prone to contact with pathogenic as well as non-pathogenic microbes, therefore immune recognition principles have to be tightly controlled. Here we show that human BEAS-2B bronchial epithelial cells inhibited secretion of the proinflammatory cytokines TNF-a and IL-12 by monocytes, macrophages and dendritic cells. This inhibitory effect could be transferred by supernatant of resting BEAS-2B cells and was also observed when primary murine tracheal epithelial cells were prepared. In contrast to inhibition of pro-inflammatory cytokine secretion epithelial cell-conditioned dendritic cells showed increased expression of IL-10 and arginase-1, thus displaying properties of alternative activation. Accordingly, Toll-like receptor-mediated up-regulation of CD40, CD86 and PD-L2 (CD273) on murine dendritic cells was reduced in the presence of bronchial epithelial cell supernatant. However, expression of negative regulatory PD-L1 (CD274) was increased and dendritic cell induced proliferation of T lymphocytes was diminished. Epithelial cells also showed a direct inhibitory effect on T lymphocyte proliferation and this was due to the constitutive secretion of TGF-b by bronchial epithelial cells. Moreover, epithelial cell-conditioned T lymphocytes showed increased differentiation towards IL-10-producing Tr1 cells. The results indicate that bronchial epithelial cells induce a noninflammatory microenvironment that regulates local immune homeostasis.

Non-hematopoietic cells contribute to protective tolerance to Aspergillus fumigatus via a TRIF pathway converging on IDO

“…10 Although ECs were found to induce Treg expansion, 13,14,40 restrained CD4 1 T-cell expansion in response to Aspergillus, 19 and produce IL-10 (this study), the therapeutic effects of kynurenines will undoubtedly cover IDO deficiency also in DCs. As a matter of fact, the highly polarized Th2/Th17 responses seen in Trif 2/2 mice are immunological features compatible with the functional program activated in lung DCs by the TRIF pathway.…”

“…[10][11][12] No longer considered innocent bystanders, 13 airway epithelial cells (ECs) are central participants in innate and adaptive immune responses as well as mucosal inflammation and allergy. 14 Through the activation of Toll-like receptors (TLRs) by endogenous and exogenous ligands, ECs may play a central role in determining the balance between a state of 'mucosal homeostasis', as is required for optimal organ function, and 'mucosal injury', leading to mucosal inflammation and barrier breakdown. 13 Recent evidence indicated that ECs may also contribute to immunity to respiratory pathogens.…”

The Tobacco Smoke Component, Acrolein, Suppresses Innate Macrophage Responses by Direct Alkylation of c-Jun N-Terminal Kinase

“…Transcriptional profiling of AMs in smokers has indicated a marked macrophage reprogramming in smokers (3,4), with suppression of inflammatory genes associated with classical M1-related inflammatory/immune genes and induction of genes associated with various M2-polarization programs relevant to tissue remodeling and immunoregulation, findings that are consistent with reduced innate immune responses and increased susceptibility to respiratory infections in smokers or CS-exposed individuals (2,5). Actions of CS on airway epithelial cells affect their production of inflammatory or host defense mediators (6)(7)(8)(9) and their interactions with DCs (10,11). Furthermore, direct actions of CS on DCs may affect DC maturation (12) and polarize T helper (Th) 2 immune responses (13,14).…”

Dendritic cell functional properties in a three-dimensional tissue model of human lung mucosa

“…Furthermore, the results from our study also demonstrate that soluble components secreted by 3D organotypic models are responsible for the enhanced production of CCL18 in DC. Although, differential expression of cytokines and chemokines by DC in response to monolayer of lung epithelial cells has been observed (26,29), the effect of 3D tissue models on DC function is limited. Therefore, we investigated whether there are differences between the 3D organotypic model, AE epithelial cells, AE fibroblasts, or submerged monolayer culture of epithelial cells and fibroblasts in terms of altering the capacity of DC to produce CCL18.…”