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Immune responses play an important role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the characteristics of T lymphocyte subsets in PCOS remain insufficiently understood. In this study, lymphocytes of follicular fluid (FF) were obtained from oocyte retrieval before in-vitro fertilization (IVF) in infertile women with or without PCOS. The levels of cluster of differentiation 25 (CD25), CD69, programmed death 1 (PD-1), interferon-γ (IFN-γ), interleukin 17A (IL-17A) and IL-10 in T lymphocytes were determined by flow cytometry. Our results showed that the percentage of FF CD8 + T cells was significantly decreased in infertile patients with PCOS ( P  < 0.05). Furthermore, the levels of CD69 and IFN-γ were significantly decreased and the level of PD-1 was increased in both CD4 + and CD8 + T cells from infertile patients with PCOS ( P  < 0.05). Moreover, the expression of PD-1 on CD4 + or CD8 + T cells was positively correlated with the estradiol (E2) levels in the serum and reversely correlated with the expression of IFN-γ in CD4 + or CD8 + T cells in infertile patients with PCOS. These results suggested that T cell dysfunction may be involved in the pathogenesis of PCOS.

Toll-like receptors (TLRs) play an important role in the induction of innate and adaptive immune responses against Schistosoma japonicum ( S . japonicum ) infection. However, the role of Toll-like receptor 7 (TLR7) in the mouse lung during S . japonicum infection and the myeloid-derived suppressor cells (MDSCs) affected by the absence of TLR7 are not clearly understood. In this study, the results indicated that the MDSCs were accumulated and the proportion and activation of CD4 + and CD8 + T cells were decreased in the lung of mice at 6–7 weeks after S . japonicum infection. Then, the expression of TLR7 was detected in isolated pulmonary MDSCs and the results showed that the expression of TLR7 in MDSCs was increased after infection. Furthermore, TLR7 agonist R848 could down-regulate the induction effect of the soluble egg antigen (SEA) on pulmonary MDSCs in vitro. Meanwhile, TLR7 deficiency could promote the pulmonary MDSCs expansion and function by up-regulating the expression of PD-L1/2 and secreting of IL-10 in the mice infected with S . japonicum . Mechanistic studies revealed that S . japonicum infection and the antigen effects are mediated by NF-κB signaling. Moreover, TLR7 deficiency aggravates S . japonicum infection-induced damage in the lung, with more inflammatory cells infiltration, interstitial dilatation and granuloma in the tissue. In summary, this study indicated that TLR7 signaling inhibits the accumulation and function of MDSCs in S . japonicum infected mouse lung by down-regulating the expression of PD-L1/2 and secreting of IL-10, via NF-κB signaling.

Despite the paramount role of TLRs in the induction of innate immune and inflammatory responses, there is a paucity of studies on the role of TLRs in Schistosoma japonicum infection. Here, we observed obvious infiltration of inflammatory cells in S. japonicum-infected C57BL/6 mouse lungs. Expression and release of IFN-γ, IL-4, and IL-17 were significantly higher in pulmonary lymphocytes from infected mice compared with control mice in response to anti-CD3 plus anti-CD28 mAbs. Higher percentages of TLR2, TLR3, TLR4, and TLR7 were expressed on such lymphocytes, and the TLR agonists PGN, Poly I:C, LPS, and R848 induced a higher level of IFN-γ. However, a higher level of IL-4 was found in the supernatant of pulmonary lymphocytes from infected mice stimulated by these TLR agonists plus CD3 Ab. Only R848 plus anti-CD3 mAb could induce a higher level of IFN-γ in such lymphocytes. TLR expressions were then compared on different pulmonary lymphocytes after infection, including T cells, B cells, NK cells, NKT cells, and γδT cells. The expression levels of TLR3 on T cells, B cells, NK cells, and γδT cells were increased in the lungs after infection. NK cells also expressed higher levels of TLR4 after infection of control mice. Collectively, these findings highlight the potential role of TLR expression in the context of S. japonicum infection.

Background Malaria has high morbidity and mortality rates in some parts of tropical and subtropical countries. Besides respiratory and metabolic function, lung plays a role in immune system. γδT cells have multiple functions in producing cytokines and chemokines, regulating the immune response by interacting with other cells. It remains unclear about the role of γδT cells in the lung of mice infected by malaria parasites. Methods Flow cytometry (FCM) was used to evaluate the frequency of γδT cells and the effects of γδT cells on the phenotype and function of B and T cells in Plasmodium yoelii -infected wild-type (WT) or γδTCR knockout (γδT KO) mice. Haematoxylin-eosin (HE) staining was used to observe the pathological changes in the lungs. Results The percentage and absolute number of γδT cells in the lung increased after Plasmodium infection ( p  < 0.01). More γδT cells were expressing CD80, CD11b, or PD-1 post-infection ( p  < 0.05), while less γδT cells were expressing CD34, CD62L, and CD127 post-infection ( p  < 0.05). The percentages of IL-4 + , IL-5 + , IL-6 + , IL-21 + , IL-1α + , and IL-17 + γδT cells were increased ( p  < 0.05), but the percentage of IFN-γ-expressing γδT cells decreased ( p  < 0.05) post-infection. The pathological changes in the lungs of the infected γδT KO mice were not obvious compared with the infected WT mice. The proportion of CD3 + cells and absolute numbers of CD3 + cells, CD3 + CD4 + cells, CD3 + CD8 + cells decreased in γδT KO infected mice ( p  < 0.05). γδT KO infected mice exhibited no significant difference in the surface molecular expression of T cells compared with the WT infected mice ( p  > 0.05). While, the percentage of IFN-γ-expressing CD3 + and CD3 + CD8 + cells increased in γδT KO infected mice ( p  < 0.05). There was no significant difference in the absolute numbers of the total, CD69 + , ICOS + , and CD80 + B cells between the WT infected and γδT KO infected mice ( p  > 0.05). Conclusions The content, phenotype, and function of γδT cells in the lung of C57BL/6 mice were changed after Plasmodium infection. γδT cells contribute to T cell immune response in the progress of Plasmodium infection.

The accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles to achieve an appropriate anti-tumor immune response and successful tumor immunotherapy. MDSCs in tumor-bearing hosts are primarily polymorphonuclear (PMN-MDSCs). However, the mechanisms regulating the development of MDSCs remain poorly understood. In this report, we showed that interferon regulatory factor 4 (IRF4) plays a key role in the development of PMN-MDSCs, but not monocytic MDSCs. IRF4 deficiency caused a significant elevation of PMN-MDSCs and enhanced the suppressive activity of PMN-MDSCs, increasing tumor growth and metastasis in mice. Mechanistic studies showed that c-Myc was up-regulated by the IRF4 protein. Over-expression of c-Myc almost abrogated the effects of IRF4 deletion on PMN-MDSCs development. Importantly, the IRF4 expression level was negatively correlated with the PMN-MDSCs frequency and tumor development but positively correlated with c-Myc expression in clinical cancer patients. In summary, this study demonstrated that IRF4 represents a novel regulator of PMN-MDSCs development in cancer, which may have predictive value for tumor progression.

Liver granulomatous inflammation and fibrosis were the primary pathological changes observed during Schistosoma japonicum (S. japonicum) infection. In the present study, the characteristics of IL-9 were investigated in the liver of S. japonicum infection C57BL/6 mice. Immunofluorescence, qRT-PCR, and ELISA results demonstrated that the expression of IL-9 significantly increased after infection ( P  < 0.01). FACS results indicated that the peak of IL-9 + Th9 cells in the liver mononuclear cells appeared at the early phase of infection (week 5), except that Th9 cells, CD8 + Tc cells, NKT and γδT cells could secrete IL-9 in this model. Although IL-9 neutralization has a limited effect on liver granulomatous inflammation, it could decrease the level of fibrosis-associated factor, PC-III, in the serum of infected mice ( P  < 0.05). Taken together, our results indicated that IL-9 was an important type of cytokine involved in the progression of S. japonicum infection-induced hepatic damage.

B cells played an important role in Schistosoma infection-induced diseases. TLR7 is an intracellular member of the innate immune receptor. The role of TLR7 on B cells mediated immune response is still unclear. Here, C57BL/6 mice were percutaneously infected by S . japonicum for 5–6 weeks. The percentages and numbers of B cells increased in the infected mice ( p < 0.05), and many activation and function associated molecules were also changed on B cells. More splenic cells of the infected mice expressed TLR7, and B cells were served as the main cell population. Moreover, a lower level of soluble egg antigen (SEA) specific antibody and less activation associated molecules were found on the surface of splenic B cells from S . japonicum infected TLR7 gene knockout (TLR7 KO) mice compared to infected wild type (WT) mice ( p < 0.05). Additionally, SEA showed a little higher ability in inducing the activation of B cells from naive WT mice than TLR7 KO mice ( p < 0.05). Finally, the effects of TLR7 on B cells are dependent on the activation of NF-κB p65. Altogether, TLR7 was found modulating the splenic B cell responses in S . japonicum infected C57BL/6 mice.

Background Recent studies have shown that CD103 is an important marker for tissue-resident memory T cells (TRM) which plays an important role in anti-infection. However, the role of CD103 + TRM was not elucidated in the progress of S. japonicum infection induced disease. Methods 6–8 weeks old C57BL/6 mice were infected by S. japonicum . Mice were sacrificed and the lungs were removed 5–6 weeks after infection. Immunofluorescent staining and Q-PCR were performed to identify the expression of CD103 molecule. Single cellular populations were made, percentages of CD103 on both CD4 + and CD8 + T lymphocytes were dynamical observed by flow cytometry (FCM). Moreover, the expression of memory T cells related molecules CD69 and CD62L, T cell function associated molecules CD107a, IFN-γ, IL-4, IL-9, and IL-10 were compared between CD103 + CD4 + and CD8 + T cells by FCM. Results CD103 + cells were emerged in the lung of both naive and S. japonicum infected mice. Both the percentage and the absolute numbers of pulmonary CD4 + and CD8 + cells were increased after S. japonicum infection ( P  < 0.05). The percentage of CD103 + cells in CD8 + T cells decreased significantly at the early stage of S. japonicum infection ( P  < 0.05). Increased CD69, decreased CD62L and CD107a expressions were detected on both CD4 + and CD8 + CD103 + T cells in the lungs of infected mice ( P  < 0.05). Compared to CD8 + CD103 + T cells, CD4 + CD103 + T cells from infected mice expressed higher level of CD69 and lower level CD62L molecules ( P  < 0.05). Moreover, higher percentage of IL-4 + , IL-9 + and IL-10 + cells on CD4 + CD103 + pulmonary T cells was found in infected mice ( P  < 0.05). Significantly increased IL-4 and IL-9, and decreased IFN-γ expressing cells were detected in CD8 + CD103 + cells of infected mice ( P  < 0.05). Conclusions CD103-expressing pulmonary CD4 + and CD8 + T cells play important roles in mediating S. japonicum infection induced granulomatous inflammation in the lung.

CD4 T follicular helper (Tfh) cells, a new subset of immune cells, have been demonstrated to be involved in granulomatous responses to infection. However, the role and underlying mechanisms of Tfh cell aggregation in infection remain incompletely understood. In this study, we provide evidence that infection enhances the accumulation of Tfh cells in the spleen, lymph nodes, and peripheral blood of C57BL/6 mice. Infection-induced Tfh cells exhibited more potent effects directly on B cell responses than the control Tfh cells ( < 0.05). Furthermore, reduced apoptosis of Tfh cells was found both in infected mice and in soluble egg antigen (SEA) treated Tfh cells ( < 0.05). Mechanistic studies reveal that caspase-3 is the primary drivers of down-regulated apoptotic Tfh cell death in infection. In summary, this study demonstrates that Tfh cell accumulation might have an impact on the generation of immune responses in infection, and caspase-3 signaling mediated apoptosis down-regulation might responsible for the accumulation of Tfh cell in this course.

Many kinds of lymphocytes are involved in ( ) infection-induced disease. γδ T cells comprise a small number of innate lymphocytes that quickly respond to foreign materials. In this study, the role of γδ T cells in the lung of -infected C56BL/6 mice was investigated. The results demonstrated that infection induces γδ T cell accumulation in the lung, expressing higher levels of CD25, MHCII, CD80, and PDL1, and lower levels of CD127 and CD62L ( < 0.05). The intracellular cytokines staining results illustrated higher percentages of IL-4-, IL-10-, IL-21-, and IL-6-producing γδ T cells and lower percentages of IFN-γ-expressing γδ T cells in the lung of infected mice ( < 0.05). Moreover, the granuloma size in lung tissue was significantly increased in Vδ mice ( < 0.05). In the lung of -infected Vδ mice, both type 1 and type 2 immune responses were decreased significantly ( < 0.05). In addition, the expression of CD80 and CD69 on B cells was decreased significantly ( < 0.05), and the SEA-specific antibody was markedly decreased ( < 0.05) in the blood of infected Vδ mice. In conclusion, this study indicates that γδ T cells could adjust the Th2 dominant immune response in the lung of -infected mice.