Effect of Dental Follicle Mesenchymal Stem Cell on Th1 and Th2 Derived Naive T Cells in Atopic Dermatitis Patients (original) (raw)
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Stimulation of T cells by autologous mononuclear leukocytes and epidermal cells in psoriasis
Archives of Dermatological Research, 1986
We found that the AMLR in psoriasis (n = 11) was similar to that in healthy controls (n = 16); furthermore, cell proliferation was alike in the presence of either 5% AB-serum or antologous serum. By contrast, while the AMECLR in healthy controls (n = 9) resembled that in psoriatics employing epidermal cells from univolved skin, epidermal cells from lesional sites (n = 10) induced a significantly higher proliferation of autologous T cells in the AMECLR (P < 0.01). We conclude that the in vitro stimulation of T cells by non-T mononuclear leukocytes is normal in psoriasis and is not regulated by autologous serum. Lesional psoriatic epidermal cells, however, are more active in stimulating autologons T cell proliferation than cells from univolved psoriatic or normal epidermis.
Journal of Investigative Dermatology, 2009
Myeloid dermal dendritic cells (DCs) accumulate in chronically inflamed tissues such as psoriasis. The importance of these cells for psoriasis pathogenesis is suggested by comparative T cell and DC cell counts, where DCs outnumber T cells. We have previously identified CD11c + BDCA-1 + cells as the main resident dermal DC population found in normal skin. We now show that psoriatic lesional skin has two populations of dermal DCs: 1) CD11c + BDCA-1 + cells which are phenotypically similar to those contained in normal skin, and 2) CD11c + BDCA-1 − cells which are phenotypically immature and produce inflammatory cytokines. While BDCA-1 + DCs are not increased in number in psoriatic lesional skin compared to normal skin, BDCA-1 − DCs are increased 30-fold. For functional studies, we FACS-sorted psoriatic dermal single cell suspensions to isolate these two cutaneous DC populations, and cultured them as stimulators in an allo-MLR. Both BDCA-1 + and BDCA-1 − myeloid dermal DC populations induced T cell proliferation, and polarized T cells to become Th1 and Th17 cells. In addition, psoriatic dermal DCs induced a population of activated T cells that simultaneously produced IL-17 and IFN-γ, which was not induced by normal skin dermal DCs. As psoriasis is believed to be a mixed Th17/Th1 disease, it is possible that induction of these IL-17 + IFNγ + cells is pathogenic. These cytokines, the T cells that produce them, and the inducing inflammatory DCs may all be important new therapeutic targets in psoriasis.
Anti-Inflammatory Effects of M-MSCs in DNCB-Induced Atopic Dermatitis Mice
Biomedicines
Atopic dermatitis (AD) is an inflammatory skin disease caused by an imbalance between Th1 and Th2 cells. AD patients suffer from pruritus, excessive dryness, red or inflamed skin, and complications such as sleep disturbances and depression. Although there are currently many AD treatments available there are insufficient data on their long-term stability and comparative effects. Moreover, they have limitations due to various side effects. Multipotent mesenchymal stem cells (M-MSCs) might have potential for next-generation AD therapies. MSCs are capable of immune function regulation and local inflammatory response inhibition. M-MSCs, derived from human embryonic stem cells (hESC), additionally have a stable supply. In L507 antibody array, M-MSCs generally showed similar tendencies to bone marrow-derived mesenchymal stem cells (BM-MSCs), although the immunoregulatory function of M-MSCs seemed to be superior to BM-MSCs. Based on the characteristics of M-MSCs on immunoregulatory function...
Journal of Investigative Dermatology, 2013
Although CD4 þ T cells are known to contribute to the pathology of atopic dermatitis (AD) and psoriasis, the role of CD8 þ T cells in these diseases remains poorly characterized. The aim of this study was to characterize the cytokine production of T cells from AD and psoriasis skin. We found that CD4 þ T cells isolated from AD skin were largely Th2 (T helper type 2) biased, in agreement with prior reports. However, we also observed large numbers of CD8 þ T cells producing IL-13, IFN-g, and IL-22. We observed increased numbers of CD8 þ T cells isolated from AD skin, and immunohistochemistry studies confirmed the presence of CD8 þ T cells in the dermis and epidermis of AD skin lesions. Surprisingly, T-cell cytokine production was similar in the lesional and nonlesional skin of patients with AD. T cells from psoriatic lesional skin predominantly produced IFN-g, IL-17, and IL-22, in agreement with prior studies. However, in addition to Th17 cells, we observed high percentages of CD8 þ T cells that produced both IL-22 and IL-17 in psoriatic skin lesions. Our findings demonstrate that CD8 þ T cells are a significant and previously unappreciated source of inflammatory cytokine production in both AD and psoriasis.
Archives of Dermatology, 2002
Background: In several open-label studies, recombinant human interleukin 10 (rhIL-10), a type 2 antiinflammatory cytokine, has been reported to improve psoriasis, a disease characterized by type 1 cytokine inflammation. Objective: To evaluate the safety, efficacy, and immunologic parameters in individuals with psoriasis treated with rhIL-10. Design and Intervention: Patients received rhIL-10 (20 µg/kg) or placebo subcutaneously 3 times weekly for 12 weeks in a randomized, double-blind manner. Setting and Patients: National Institutes of Health Clinical Center in Bethesda. Twenty-eight patients with moderate-to-severe psoriasis as defined by a Psoriasis Area Severity Index (PASI) score of 10 or higher. Main Outcome Measure: The primary clinical end point was the mean percentage change in the PASI score comparing baseline and week 12 scores. Intracellular cy-tokine production by peripheral blood mononuclear cells (PBMCs) was measured by flow cytometry. Results: There was no significant difference in the mean percentage change in the PASI score from baseline to week 12 between the rhIL-10-treated group and control patients (17% vs 13% improvement, respectively; P=.69), although a modest trend toward improvement in patients receiving rhIL-10 was documented at both the 6and 8-week points. Interestingly, proinflammatory and type 1 cytokine production by PBMCs progressively declined in the rhIL-10-treated patients during the entire 12-week study period. Conclusions: Treatment with rhIL-10 resulted in only temporary clinical improvement in psoriasis, despite sustained systemic decreases in proinflammatory and type 1 cytokine production. These data suggest that immunotherapy that decreases the ratio of systemic type 1 and type 2 cytokine production does not necessarily lead to improvement of type 1 cytokine-mediated disease.
Allergologia et Immunopathologia, 2019
Background: House dust mite (Dermataphagoides pteronyssinus) is a widespread risk factor in the development of asthma. CD4 + T lymphocytes have an important role in the pathogenesis of allergic asthma by polarizing to Th2 cells. Objective: We aimed to evaluate the immunoregulatory effects of dental follicle mesenchymal stem cells with and without IFN-␥ stimulation on peripheral blood mononuclear cells of house dust mite sensitive asthmatic patients, and compared those with Dexamethasone as a systemic steroid. Material and methods: PBMC of asthmatic patients and healthy individuals separately cultured with or without DF-MSCs in the presence and absence of IFN-␥ or Der p1 or Dexamethasone for 72 h. CD4 + T proliferation, cell viability, CD4 + CD25 + FoxP3 + Treg cell frequency and cytokine profiles of PBMC were evaluated via flow cytometry. Results: DF-MSCs suppressed proliferation of CD4 + T lymphocytes (p CDmix < 0.01, p Derp1 < 0.01, p IFN < 0.005) by increasing the number of FoxP3 expressing CD4 + CD25 + T regulatory cells (p CDmix < 0.005, p Derp1 < 0.01, p IFN < 0.001) and suppressed lymphocyte apoptosis (p CDmix < 0.05, p Derp1 < 0.05, p IFN < 0.05), while Dexamethasone increased the apoptosis and decreased Treg cell frequency in asthmatic patients. IFN-␥ stimulation increased the suppressive effect of DF-MSCs and also enhanced the frequency of FoxP3 expressing CD4 + CD25 + T regulatory cells. The cytokine levels were regulated by DF-MSCs by reducing IL-4 cytokine levels (p CDmix < 0.01, p Derp1 < 0.05, p IFN < 0.05) and upregulating IFN-␥ levels (p CDmix < 0.01, p Derp1 < 0.05, p IFN < 0.005) in asthmatic patients.
Systemic immune mechanisms in atopic dermatitis and psoriasis with implications for treatment
Experimental Dermatology
Atopic dermatitis (AD) and psoriasis are inflammatory skin diseases that negatively affect patients' quality of life. Although distinctions exist between these diseases, both are characterized by erythematous, thickened epidermal lesions that vary in intensity and affected body surface area. Early models of aetiology attributed symptoms of both diseases to cutaneous inflammation at lesion sites, but recent studies have established that activated immune mediators in the circulation drive disease severity. Activation of T helper 2 (Th2) and Th22 cells in the circulation appears to be the principal initiator of acute AD pathology, with the emergence of Th1 and Th17/interleukin (IL)-23 pathway activation marking the transition to a chronic state. The Th17/IL-23 pathway also has an important role in psoriasis. The role of systemic inflammation in AD and psoriasis is supported by the occurrence of non-cutaneous comorbidities that affect patients, most of which intensify morbidity and disability associated with lesional skin. Atopic dermatitis is associated with allergic disorders consisting of the "atopic march," whereas psoriasis is frequently accompanied by psoriatic arthritis. Patients with both disorders are at significantly higher risk of obesity, metabolic disorders, and cardiovascular diseases, all of which feature inflammatory components in their pathology models. These insights have led to novel therapeutics aimed at addressing psoriasis by targeting tumor necrosis factor-and Th17-related cytokine pathways. The success of these agents in psoriasis management is driving new therapeutic approaches for moderate-to-severe AD, including agents targeting the Th2 and Th17/ Th22 cytokine pathways.
Clinical & Experimental Immunology
Summary 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-MS...