Dental follicle mesenchymal stem cells down-regulate Th2-mediated immune response in asthmatic patients mononuclear cells.

BACKGROUND: Asthma is a chronic inflammatory disease in which inflammatory responses have the polarisation of CD4+ T cells to Th2 cells. Dental follicle mesenchymal stem cells (DFSCs) have strong anti-inflammatory properties comparable to other mesenchymal stem cells. OBJECTIVE: We investigated the immunomodulatory effects of DFSCs on CD4+ T helper cell responses of asthmatic patients and compared the results with those obtained with asthmatic subjects on immunotherapy and with healthy individuals. METHOD: Peripheral blood mononuclear cells (PBMC) were isolated from immunotherapy naïve asthmatics, asthmatics on subcutaneous Der p1 immunotherapy and from healthy individuals. PBMC were pre-conditioned with anti-CD3/anti-CD28 mAbs, Der p1 or IFN-γ in the presence and absence of DFSCs and analysed for T cell viability and proliferation, CD4+ CD25+ FOXP3+ regulatory T cell frequencies, cytokine expression, and GATA3, T bet and FoxP3 expressions. Neutralisation of TGF-ß and blockade of IDO and PGE2 pathways were performed to determine suppressive signalling pathways of DFSCs. RESULTS: Dental follicle mesenchymal stem cells suppressed proliferative responses of CD4+ T lymphocytes and increased the frequency of Treg cells. DFSCs decreased effector and effector memory CD4+ T cell phenotypes in favour of naïve T cell markers. DFSCs decreased IL-4 and GATA3 expression and increased IFN-γ, T-bet and IL-10 expression in asthmatics. Costimulatory molecules were suppressed in monocytes with DFSCs in the cocultures. DFSCs down-regulated inflammatory responses via IDO and TGF-ß pathways in asthmatic patients. CONCLUSION: Dental follicle mesenchymal stem cells suppressed allergen-induced Th2-cell polarisation in favour of Th1 responses and attenuated antigen-presenting cell co-stimulatory activities. These studies suggest that DFSC-based cell therapy may provide pro-tolerogenic immunomodulation relevant to allergic diseases such as asthma.

Alteration in humoral immunity is common among family members of patients with common variable immunodeficiency.

BACKGROUND: The prevalence of primary immunodeficiency (PID) in the relatives of patients with common variable immunodeficiency (CVID) and IgA deficiency is high. Allergic disorders have been recorded in patients with humoral immunodeficiency. We aimed to determine the frequency of humoral immunodeficiency and atopy in the relatives of patients with CVID. METHODS: The study population comprised 20 CVID patients and their relatives. All relatives were screened using a questionnaire covering demographic characteristics, warning signs of PID (adults and children), and core questions on asthma, rhinitis, and eczema from the International Study of Asthma and Allergies in Childhood (ISAAC). We also recorded absolute neutrophil and lymphocyte counts, serum immunoglobulin levels, pulmonary function values, and skin prick test results. RESULTS: The study sample comprised 20 patients with CVID (15 males, 5 females; mean (SD] age, 16.4 (9] years) and 63 first-degree relatives (18 mothers, 16 fathers, 16 sisters, 10 brothers, and 3 offspring). The rate of parental consanguinity was 75%. Of 17 family members with positive PID warning signs, 6 had concomitant hypogammaglobulinemia (3 low IgM levels, 2 selective IgA deficiency, and 1 partial IgA deficiency). The ISAAC questionnaire revealed allergic rhinitis in 3 mothers, asthma in 2 fathers, and 1 sibling. Skin prick testing revealed sensitization to aeroallergens in 31.6% of cases in addition to 1 parent and 1 sibling. CONCLUSIONS: Almost half of the 20 families with a CVID patient had at least 1 additional member with hypogammaglobulinemia, leading us to recommend routine screening for relatives of CVID patients.