Dendritic cells from aged subjects contribute to chronic airway inflammation by activating bronchial epithelial cells under steady state

Prakash, Sangeetha; Agrawal, Sudhanshu; Vahed, Hawa; Ngyuen, M; BenMohamad, L; Gupta, Sudhir; Agrawal, Anshu

doi:10.1038/mi.2014.28

Cited by 35 publications

(35 citation statements)

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“…Alterations in the functions of AECs at homeostasis may therefore modulate the response of DCs to infections. A previous study from our laboratory has demonstrated that inflammatory DCs from elderly individuals can modulate the function of AECs at homeostasis . Taken together, these studies suggest that interaction of AECs and DCs at homeostasis plays a major role in maintaining immunity and tolerance in the airways.…”

Section: Discussionsupporting

confidence: 62%

“…Mucus secretion was also observed by the cells. At this time these cells also displayed high level transepithelial electrical resistance (TEER) and resistance to dextran fluorescein isothiocyanate (FITC) migration measured as described earlier .…”

Section: Methodsmentioning

confidence: 54%

“…For example, during infection, proinflammatory cytokine secretion by DCs not only increases the permeability of the epithelial cell barrier to allow infiltration of other immune cells, but also up‐regulates the expression anti‐microbial peptides in AECs . Furthermore, we have demonstrated previously that DCs from elderly individuals produce spontaneously high levels of damaging proinflammatory mediators which promote the secretion of various chemokines from AECs, resulting in enhanced airway inflammation . As DCs influence epithelial cells, so do AECs impact DC functions .…”

Section: Introductionmentioning

confidence: 99%

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Airway epithelial cells enhance the immunogenicity of human myeloid dendritic cells under steady state

Agrawal

Srivastava

Rahmatpanah

et al. 2017

Clinical and Experimental Immunology

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SummaryDendritic cells (DCs) and airway epithelial cells (AECs) are in close proximity, and AECs secrete factors such as retinoic acid which induce tolerance in DCs at homeostasis. However, the question remains as to how DCs in the lung are able to respond to pathogens in the immunosuppressive environment. Using an in vitro human myeloid DC (mDC)-AEC co-culture system, we demonstrate that AECs induced several gene changes in the mDCs cultured with AECs compared to the mDCs not cultured with AECs. Analysis revealed that several chemokine genes were altered. These chemokine genes could serve to attract neutrophils, natural killer (NK) T as well as T helper type 1 (Th1)/Th2 cells to the airways. Genes priming lipid and major histocompatibility complex (MHC) class II antigen presentation were also up-regulated, along with certain anti-microbial protein genes. In addition, the expression and function of pathogen-sensing Toll-like receptors (TLRs) as well as Nod-like receptors (NLRs) and their downstream signalling molecules were up-regulated in mDCs cultured with AECs. Moreover, murine mucosal DCs from the lung expressed significantly higher levels of TLRs and NLRs compared to peripheral DCs from the spleen. These results indicate that AECs prime mDCs to enhance their immunogenicity, which could be one of the mechanisms that compensates for the immunosuppressive mucosal environment.

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Section: Discussionsupporting

confidence: 62%

Section: Methodsmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 99%

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Airway epithelial cells enhance the immunogenicity of human myeloid dendritic cells under steady state

Agrawal

Srivastava

Rahmatpanah

et al. 2017

Clinical and Experimental Immunology

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“…Recently, it has been proved that the dendritic cells (DCs) in the elderly have an activated phenotype and an increased secretion of pro-inflammatory cytokines, which are responsible for the infiltration of eosinophils, the airway remodeling and the increase of asthma and chronic respiratory diseases [ 47 ]. In the SLIT the oral DCs are the first structures involved in the mechanism, with the aim to modulate the allergen-specific antibody responses.…”

Section: Reviewmentioning

confidence: 99%

Choosing wisely: practical considerations on treatment efficacy and safety of asthma in the elderly

et al. 2015

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The prevalence of asthma in the most advanced ages is similar to that of younger ages. However, the concept that older individuals may suffer from allergic asthma has been largely denied in the past, and a common belief attributes to asthma the definition of “rare” disease. Indeed, asthma in the elderly is often underdiagnosed or diagnosed as COPD, thus leading to undertreatment of improper treatment. This is also due to the heterogeneity of clinical and functional presentations of geriatric asthma, including the partial loss of reversibility and the lower occurrence of the allergic component in this age range. The older asthmatic patients are also characterized the coexistence of comorbid conditions that, in conjunction with age-associated structural and functional changes of the lung, may contribute to complicate the management of asthma. The current review addresses the main issues related to the management of allergic asthma in the geriatric age. In particular, the paper aims at revising current pharmacological and non pharmacological treatments for allergic asthmatics of advanced ages, primarily focusing on their safety and efficacy, although most behaviors are an arbitrary extrapolation of what has been tested in young ages. In fact, age has always represented an exclusion criterion for eligibility to clinical trials. Experimental studies and real life observations specifically testing the efficacy and safety of therapeutic approaches in allergic asthma in the elderly are urgently needed.

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“…Viceversa , in the presence of injurious stimuli ( e.g., viruses and bacteria) elevated basal production of cytokines hampers release of pro-inflammatory mediators, as observed in aged and knockout animals [ 19 – 26 ]. Just recently, old dendritic cells (DCs) have been shown to contribute to chronic airway inflammation, releasing pro-inflammatory mediators, mostly tumor necrosis factor (TNF)-α, which affects primarily bronchial epithelial cell function in vitro, enhancing the epithelial barrier permeability, thus increasing susceptibility to infectious respiratory disease in ageing [ 27 ]. Finally, naïve CD4 + and CD8 + cells are reduced in aged animals and humans with an impaired conversion towards memory cells able to respond to new antigens in the context of respiratory tract [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of thermal water inhalation in chronic upper respiratory tract infections in elderly and young patients

et al. 2016

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BackgroundChronic upper respiratory tract infections (cURTI) are very frequent illnesses which occur at any age of life. In elderly, cURTI are complicated by immunosenescence, with involvement of lung immune responsiveness.ResultsIn the present study, 51 elderly (age range: 66–86) and 51 young (age range 24–58) cURTI patients underwent a single cycle (two weeks) of inhalatory therapy with salt-bromide-iodine thermal water in the thermal station “Margherita di Savoia” (Margherita di Savoia, BAT, Italy). Peripheral blood serum cytokines and clinical assessment were performed before therapy (T0) and after six months (T1) and 12 months (T2) from inhalatory treatment. In both elderly and young patients, at baseline an increased release of T helper (h)1-related cytokines [interleukin (IL)-2 and interferon-γ] and of Th2-related cytokine (IL-4) was documented. Inhalatory treatment reduced the excessive secretion of all the above-cited cytokines. IL-10 values were above normality at all times considered in both groups of patients. In addition, an increase in IL-17 and IL-21 serum levels following therapy was observed in both groups of patients. Pro-inflammatory cytokine (IL-1β, IL-6, IL-8 and tumor necrosis factor-α) baseline values were lower than normal values at T0 in both elderly and young cURTI patients. Their levels increased following inhalatory treatment.Clinically, at T2 a dramatic reduction of frequency of upper respiratory tract infections was recorded in both groups of patients.ConclusionThermal water inhalation is able to modulate systemic immune response in elderly and young cURTI patients, thus reducing excessive production of Th1 and Th2-related cytokines, on the one hand. On the other hand, increased levels of IL-21 (an inducer of Th17 cells) and of IL-17 may be interpreted as a protective mechanism, which likely leads to neutrophil recruitment in cURTI patients. Also restoration of pro-inflammatory cytokine release following inhalatory therapy may result in microbe eradication. Quite importantly, the maintenance of high levels of IL-10 during the follow-up would suggest a consistent regulatory role of this cytokine in attenuating the pro-inflammatory arm of the immune response.

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Dendritic cells from aged subjects contribute to chronic airway inflammation by activating bronchial epithelial cells under steady state

Cited by 35 publications

References 50 publications

Airway epithelial cells enhance the immunogenicity of human myeloid dendritic cells under steady state

Airway epithelial cells enhance the immunogenicity of human myeloid dendritic cells under steady state

Choosing wisely: practical considerations on treatment efficacy and safety of asthma in the elderly

Effects of thermal water inhalation in chronic upper respiratory tract infections in elderly and young patients

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