T helper (Th)1, Th17 and Th2 imbalance in mesenchymal stem cells of adult patients with atopic dermatitis: at the origin of the problem

Orciani, Monia; Campanati, Anna; Caffarini, Miriam; Ganzetti, Giulia; Consales, Veronica; Lucarini, Guendalina; Offidani, Annamaria; Primio, Roberto Di

doi:10.1111/bjd.15078

Cited by 51 publications

(65 citation statements)

References 34 publications

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“…The level of secreted cytokines at baseline confirm the imbalance of Th1/17 versus the Th2 axis also observed in our previous studies [4,8,23]: MSCs from psoriatic patients secrete higher amounts of Th1/Th17 inflammatory molecules (IL-6, IL-12, IL-13, IL-17A, TGF-b, IFN-g, TNF-a and G-CSF) than MSCs from control subjects. Conversely, IL-2 is less secreted by PsO-MSCs than H-MSCs.…”

Section: Discussionsupporting

confidence: 88%

Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells

Campanati

Orciani

Sorgentoni

et al. 2018

Clinical and Experimental Immunology

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Psoriasis microenvironment, characterized by an imbalance between T helper type 1 (Th1)/Th17 and Th2 cytokines and also influences the mesenchymal stem cells (MSCs) phenotypical profile. MSCs from healthy donors (H-MSCs) can exert a strong paracrine effect by secreting active soluble factors, able to modulate the inflammation in the microenvironment. To evaluate the influence of H-MSCs on MSCs from psoriatic patients (PsO-MSCs), H-MSCs and PsO-MSCs were isolated and characterized. Indirect co-culture of H-MSCs with PsO-MSCs was performed; effects on proliferation and expression of cytokines linked to Th1/Th17 and Th2 pathways were assayed before and after co-culture. The results show that before co-culture, proliferation of PsO-MSCs was significantly higher than H-MSCs (P < 0·05) and the levels of secreted cytokines confirmed the imbalance of Th1/Th17 versus the Th2 axis. After co-culture of H-MSCs with PsO-MSCs, healthy MSCs seem to exert a 'positive' influence on PsO-MSCs, driving the inflammatory phenotypical profile of PsO-MSCs towards a physiological pattern. The proliferation rate decreased towards values nearer to those observed in H-MSCs and the secretion of the cytokines that mostly identified the inflammatory microenvironment that characterized psoriasis, such as interleukin (IL)-6, IL-12, IL-13, IL-17A, tumour necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (G-CSF), is significantly lower in co-cultured PsO-MSCs than in individually cultured PSO-MSCs (P at least < 0·05). In conclusion, our preliminary results seem to provide an intriguing molecular explanation for the ever-increasing evidence of therapeutic efficacy of allogeneic MSCs infusion in psoriatic patients.

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Section: Discussionsupporting

confidence: 88%

Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells

Campanati

Orciani

Sorgentoni

et al. 2018

Clinical and Experimental Immunology

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“…Interestingly, psoriasis, a Th1-Th17-mediated disease [1], was found in 4% of our patients (10/253), a percentage which is similar to the psoriasis prevalence in general population, suggesting a possible overlap between Th1-Th17 and Th-2 pathways in AD, especially in adult-onset or persistent chronic forms as reported by a study conducted among Korean adults visiting health service centre in Seul [13]. Indeed, the importance of Th1-Th17 pathway in AD course is further supported by a very recent study which showed that the profile of Cutaneous Mesenchymal Stem Cells, obtained from patients suffering from chronic AD, retraces a Th1-Th17 environment [up-regulation of interleukin (IL)6, IL8, IL12, IL13, IL17A, IL17F, transforming growth factor-b, interferon-c, whereas Th2 chemokines such as IL2, IL4, IL5, and IL23A were down-regulated) [21].…”

Section: Discussionmentioning

confidence: 76%

An Italian multicentre study on adult atopic dermatitis: persistent versus adult-onset disease

et al. 2017

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Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease which predominantly affects children. However, AD may persist until adulthood (persistent AD), or directly start in adults (adult-onset AD). AD often shows a non-flexural rash distribution, and atypical morphologic variants in adults and specific diagnostic criteria are lacking. Moreover, adult AD prevalence as well as detailed data which can characterize persistent vs adult-onset subtype are scant. The aim of this study was to investigate on the main features of adult AD particularly highlighting differences between persistent vs adult-onset form. An Italian multicentre observational study was conducted between April 2015-July 2016 through a study-specific digital database. 253 adult AD patients were enrolled. Familiar history of AD was negative in 81.0%. Erythemato-desquamative pattern was the most frequent clinical presentation (74.3%). Flexural surface of upper limbs was most commonly involved (47.8%), followed by eyelid/periocular area (37.9%), hands (37.2%), and neck (32%). Hypertension (7.1%) and thyroiditis (4.3%) were the most frequent comorbidities. A subgroup analysis between persistent (59.7%) vs adult-onset AD patients (40.3%) showed significant results only regarding AD severity (severe disease was more common in persistent group, p < 0.05), itch intensity (higher in adult-onset disease), and comorbidities (hypertension was more frequent in adult-onset group, p < 0.01). Adult AD showed uncommon features such as significant association with negative AD family history and lacking of association with systemic comorbidities respect to general population. No significant differences among persistent vs adult-onset subgroup were registered except for hypertension, itch intensity, and disease severity.

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“…According to the cytokines secreted, T helper cells (Th cells) can be classified into Th1, Th2 and Th17 . Keeping Th1/Th2/Th17 balance is key to maintain body immune and inflammatory homeostasis .…”

Section: Introductionmentioning

confidence: 99%

Co‐administration of N‐acetylcysteine and dexmedetomidine plays a synergistic effect on protection of LPS‐induced acute lung injury via correcting Th1/Th2/Th17 cytokines imbalance

Qitai

Lin

Chen

et al. 2019

Clin Exp Pharma Physio

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Recently both N‐acetylcysteine (NAC) and Dexmedetomidine (DEX) have shown emerging roles in protection of acute lung injury (ALI). However, how their protective roles work and whether they can provide synergistic effects in ALI remain unknown. Here we explored it from the hot research viewpoint of Th1/Th2/Th17 cytokines balance. Lipopolysaccharide (LPS)‐induced ALI was established and treated with NAC and/or DEX. Mice were divided into Sham group, ALI group, NAC group, DEX group and NAC+DEX group. Mice were sampled at 6, 12 and 24 hours after the model construction. Histopathology, wet to dry ratio and myeloperoxidase (MPO) activity were assessed in lung tissues. Protein concentration and cell count were assessed in bronchoalveolar lavage fluid (BALF). Th1/Th2/Th17 cytokines were assessed in plasma, BALF and lung homogenate. ALI‐induced lung morphological damage, edema and aberrant MPO activity can be attenuated by NAC or DEX and mostly by NAC+DEX. NAC with DEX significantly reduced ALI‐induced protein leakage and cell infiltration in BALF. Th1/Th2/Th17 cytokines imbalance aggravated with ALI progression. NAC, DEX and especially NAC+DEX can effectively correct these unbalanced cytokines. Galectin‐9 and Tim‐3 were transcriptionally up‐regulated in ALI. Combination of NAC with DEX obtained a maximum effect on decreasing Galectin‐9/Tim‐3 expression. In summary, Th1/Th2/Th17 cytokines imbalance is newly found to participate in LPS‐induced ALI. NAC or DEX administration can attenuate ALI by rebalancing Th1/Th2/Th17 cytokines. Their protective roles can be enhanced when co‐administration, because DEX may relieve the Galectin‐9/Tim‐3 axis‐mediated immune suppression.

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T helper (Th)1, Th17 and Th2 imbalance in mesenchymal stem cells of adult patients with atopic dermatitis: at the origin of the problem

Abstract: The profile of MSCs obtained from patients with chronic AD retraces the Th1/Th17 cell environment observed in differentiated cells of chronic AD. This evidence could open a new scenario in the pathogenesis of AD, according to which the inflammatory process may involve MSCs early on.

Cited by 51 publications

References 34 publications

Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells

Indirect co-cultures of healthy mesenchymal stem cells restore the physiological phenotypical profile of psoriatic mesenchymal stem cells

An Italian multicentre study on adult atopic dermatitis: persistent versus adult-onset disease

Co‐administration of N‐acetylcysteine and dexmedetomidine plays a synergistic effect on protection of LPS‐induced acute lung injury via correcting Th1/Th2/Th17 cytokines imbalance

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