Following the stimulation, mRNA of IL17/RORC, protein secretion of IL17, and intracellular IL17 levels were upregulated in PBMCs from AR patients but not in control subjects; while the increase of Th2 but decrease of Th1 cells was also determined in all AR’s PBMCs. These results show a concordance between in vivo and in vitro findings, confirming that not only Th2, but also Th17 cells play an important role in the context of allergic inflammation. IL10 producing CD4+ T cells showed a distinct response to HDM in PBMCs among different subject groups: reduction of IL10+ cells in SIT-untreated AR, but an increase in SIT-treated and control subjects. These different reactions indicate the regulatory function of IL10+ cells may be impaired in severe inflammation, while it can be activated in mild inflammatory or healthy status, (+)-JQ1 showing a similar pattern as those found in the in vivo situation.
Although the clinical and molecular improvement was obvious in AR subjects who received SIT, the levels of IL17 as well as its related markers and the Th cell subsets show a significant difference between SIT-treated AR and controls. Moreover, allergen stimulation was able to promote the Th17 and Th2 inflammatory response in PBMCs from SIT-treated AR patients, although the change of these cytokine expressions was less than that in SIT-untreated AR. This evidence indicates the immunologic changes may not be completely normalized by a 2-year of SIT in AR. As recommended by the literature, a 3-year or longer SIT period may result in consistent long-lasting effects after the cessation of treatment. Some limitations of the current study need to be considered. After excluding the non-compliant patients and the SIT unresponsive patients, only a small number of subjects were analyzed in this study. Follow-up studies are needed in a large number of patients to verify the Th17 response between SIT responsive and unresponsive groups. Another shortcoming is the lack of controlled placebo group. For ethical reasons, it was not reasonable to have AR patients not treated with any form of pharmacologic agents for 2 years.
However, we have compared the change of molecular response in each patient before and after treatment, which could be regarded as a self-control design to minimize the placebo effect. In addition, a lack of the evidences of local nasal response is also a limitation. In conclusion, our in vivo and in vitro studies presented the evidence that not only Th2 but also Th17 mediated inflammation was involved in the AR pathological mechanism. The Th17 response was reduced in AR following SIT. The relationship between IL10 producing CD4+ T cell and Th17 immunity in AR and its response to SIT needs to be further clarified.IGF-1 has insulin-like metabolic effects. Our previous studies have found that IGF-1 acts on insulinsecreting cells, NOD mice and diabetic rats in vivo, reducing islet inflammation, promoting cell proliferation, and inhibiting against apoptosis. The key for T1D treatment is to recover the proliferation and function of endogenous islet b-cells and to prevent autoimmunity that could damage islet b-cells. In this study, we conducted combined intervention of IL-10 and IGF1 in NOD mice with diabetes at onset stage and evaluated its protective effects on the residual islet b- cells.