The inflammatory mechanisms of environmental pollutants in chronic rhinosinusitis (CRS) have recently been proposed. However, the mechanisms underlying the inflammatory effects of particulate matter (PM) on nasal polyp (NP) tissues remain unknown. Here we investigated the mechanism underlying the inflammatory effects of PM10 on human nasal polyp-derived fibroblasts (NPDFs). We isolated NPDFs from human NP tissues obtained from patients with CRS with NPs (CRSwNP). The NPDFs were exposed to PM10 in vitro. Immunologic characteristics were assessed using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, Western blot, and flow cytometry. Additionally, we investigated the effect of NPDF-conditioned media (CM) on the expression of CD4⁺ T cell inflammatory mediators. PM10-treated NPDFs significantly upregulated interleukin (IL)-6, IL-4, and IL-33 expression and CXCL1 protein levels than PM10-treated normal tissues. MAP kinase, AP-1, and NF-kB were the primary cell signaling proteins. Immune cells in NPDF-CM had elevated IL-13, IL-17A, and IL-10 expression, but no significant difference in IFN-γ, TNF-α, and IL-4 expression. Moreover, under a Th2 inducing condition, NPDF-CM-treated CD4⁺ T cells had increased expression of IL-13, IL-10, and IL-17, which was reversed on ST2 inhibitor addition. Our study suggests that PM10 exposure could significantly increase the Th2 inflammatory pathway in NP tissues, specifically the IL-33/ST2 pathway-mediated immune response.

Background: Tonsil-derived mesenchymal stem cells (T-MSCs) were reported to have suppressive effect on T cells, yet much remains unknown about the underlying mechanisms supporting this effect. We investigated the underlying mechanism of the immunomodulatory effect of T-MSCs on immune cell proliferation and cytokine production. Methods: We isolated T-MSCs from human palatine tonsil and evaluated the immunomodulatory capacity using RT-PCR, ELISA, and flow cytometry. Additionally, we assessed the expression of various soluble factors and several costimulatory molecules to detect the priming effect on T-MSCs. Results: T-MSCs significantly inhibited the immune cell proliferation and cytokine expression (TNF-α and IFN-γ) in the direct co-culture, but there was no suppressive effect in indirect co-culture. Additionally, we detected a remarkably higher expression of indoleamine 2,3-dioxygenase (IDO) in the primed T-MSCs having co-expression CD40. Moreover, immune cells or CD4⁺ T cells showed lower TNF-α, IFN-γ, and IL-4 expression when the primed T-MSC were added; whereas those findings were reversed when the inhibitor for IDO (not IL-4) or CD40 were added. Furthermore, T-bet and GATA3 levels were significantly decreased in the co-cultures of the primed T-MSCs and CD4⁺ T cells; whereas those findings were reversed when we added the neutralizing anti-CD40 antibody. Conclusions: Primed T-MSCs expressing IDO and CD40 may have immunomodulatory capacity via Th1-mediated and Th2-mediated immune response.

We used a nationwide cohort sample of data from 2002 to 2013, representing approximately 1 million patients to investigate the prospective association between migraine and dementia. The migraine group (n = 1472) included patients diagnosed between 2002 and 2004, aged over 55 years; the comparison group was selected using propensity score matching (n = 5888). Cox proportional hazards regression analyses was used to calculate the hazard ratios (HRs). The incidence of dementia was 13.5 per 1000 person-years in the migraine group. Following adjustment for sociodemographic and comorbidities variables, patients with migraine developed dementia more frequently than those in the comparison group (adjusted HR = 1.37, 95% confidence interval [CI], 1.16–1.61). In the subgroup analysis, we found a higher HR of dementia events in male, the presence of comorbidities, and older age (≥65) patients with migraine, compared to those without migraine. Moreover, patients with migraine had a significantly higher incidence of Alzheimer’s disease (adjusted HR = 1.31, 95% CI, 1.08–1.58), but not vascular dementia, than those without migraine. Therefore, our findings suggest that mid- and late-life migraines may be associated with an increased incidence of all-cause dementia and Alzheimer’s disease, but not vascular dementia.

Mesenchymal stem cells (MSCs) ameliorate T-and B cell-mediated immune responses. In particular, tonsil-MSCs (T-MSCs) are attractive candidates for practical and clinical applications because of their ease of acquisition and relatively low immunogenicity compared with other MSC sources. The use of MSCs as a therapeutic tool in atopic dermatitis (AD) has been investigated, but that of T-MSCs remains to be explored. Therefore, we investigated the immunomodulatory effects of primed T-MSCs in AD pathogenesis. In our animal study, primed T-MSCs showed greater immunological suppressive effects than naïve T-MSCs. Additionally, in vitro, the proliferation of B cells was downregulated by the addition of primed T-MSCs compared with naïve T-MSCs. The activation of B cells to differentiate into antibody-secreting cells and produce IgE was also reduced when primed T-MSCs were added. Moreover, under CD40-knockdown conditions, we found that CD40 in primed T-MSCs played a critical role as a regulator of B cell activation and was mediated by the non-canonical NF-κB pathway. Therefore, our findings suggest a promising role for primed T-MSCs in the treatment of AD by regulating B cell-mediated inflammatory responses, which are dependent on CD40 expression on primed T-MSCs mediated through the non-canonical NF-κB pathway.

Migraine is a common neurological disease that causes a variety of symptoms, most notably throbbing, which is described as a pulsing headache on one side of the head. Burning mouth syndrome (BMS) is defined as an intra-oral burning sensation. Currently, no medical or dental cause has been identified for BMS. Interestingly, neuropathic pain is a characteristic feature of BMS; however, it remains unclear whether migraine can cause BMS. We aimed to identify the association of migraine with the risk of developing BMS. We used a representative nationwide cohort sample of approximately 1 million patients from 2002 to 2013 to investigate the prospective association between migraine and BMS. A total of 4157 migraine patients (migraine group) and 16,628 patients without migraine (comparison group) were enrolled after 1:4 propensity score matching. The overall incidence of BMS was significantly higher in the migraine group (0.15 per 1000 person-years) than in the comparison group (0.05 per 1000 person-years). The adjusted HR for patients with migraine who reported BMS events during the 10-year follow-up period was 2.96 (95% confidence interval, 1.02–8.56), after adjusting for other covariates. However, in the subgroup analysis, the adjusted HR for BMS events did not show a significant difference between the migraine and comparison group according to sex, age, and comorbidities. This study suggests that migraine is associated with an increased incidence of BMS. Therefore, clinicians should be attentive to detect BMS at an early stage when treating patients with migraine.

Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin−CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.