T follicular helper cells in patients with acute schistosomiasis

Zhang, Yumei; Wang, Yanjuan; Jiang, Yanyan; Pan, Wei; Liu, Hua; Yin, Jiong; Shen, Yujuan; Cao, Jianping

doi:10.1186/s13071-016-1602-6

Cited by 16 publications

(18 citation statements)

References 28 publications

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“…Wang et al found that, in murine schistosomiasis, Tfh cells accumulate in the splenic germinal center and that the Tfh phenotypic molecule, Bcl-6, and the Tfh-type cytokine, IL-21, correlate with progression of liver fibrosis (92). In addition, clinical studies have shown that Tfh cells are involved in immune responses for both acute and chronic human schistosomiasis (93,94). The frequency of circulating PD-1 + CXCR5 + CD4 + Tfh cells in the peripheral blood is increased in both acute and chronic schistosomiasis patients relative to healthy controls.…”

Section: Tfh Promotes Liver Pathology Of Schistosomiasismentioning

confidence: 99%

“…The frequency of circulating PD-1 + CXCR5 + CD4 + Tfh cells in the peripheral blood is increased in both acute and chronic schistosomiasis patients relative to healthy controls. However, the difference between acute and chronic schistosomiasis is that there is no correlation between percentages of PD-1 + CXCR5 + CD4 + Tfh cells, memory B cells, or the level of immunoglobulin G (IgG) specific to S. japonicum antigen in acute schistosomiasis patients; however, frequency of PD-1 + CXCR5 + CD4 + Tfh cells is positively correlated to the levels of IL-21 in sera and the levels of SEA-specific antibody in chronic schistosomiasis patients (93,94). These findings demonstrate that Tfh cells might exhibit distinct mechanisms to regulate the immune response between acute and chronic schistosomiasis.…”

Section: Tfh Promotes Liver Pathology Of Schistosomiasismentioning

confidence: 99%

“…Acute schistosomiasis is recognized as a Th1-dominated disease. Recent studies showed that Th17 and Tfh are also involved in the immune response of acute cases (71,94). Chronic disease of hepatic granuloma formation and fibrosis are upregulated by Th2 and Th17 cells, mainly secreting IL-4 and IL-17, respectively (33, 63), and downregulated by Th1 and Treg cells (80,113).…”

Section: Summary and Concluding Commentsmentioning

confidence: 99%

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T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

et al. 2020

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The parasitic worms, Schistosoma mansoni and Schistosoma japonicum, reside in the mesenteric veins, where they release eggs that induce a dramatic granulomatous response in the liver and intestines. Subsequently, infection may further develop into significant fibrosis and portal hypertension. Over the past several years, uncovering the mechanism of immunopathology in schistosomiasis has become a major research objective. It is known that T lymphocytes, especially CD4 + T cells, are essential for immune responses against Schistosoma species. However, obtaining a clear understanding of how T lymphocytes regulate the pathological process is proving to be a daunting challenge. To date, CD4 + T cell subsets have been classified into several distinct T helper (Th) phenotypes including Th1, Th2, Th17, T follicular helper cells (Tfh), Th9, and regulatory T cells (Tregs). In the case of schistosomiasis, the granulomatous inflammation and the chronic liver pathology are critically regulated by the Th1/Th2 responses. Animal studies suggest that there is a moderate Th1 response to parasite antigens during the acute stage, but then, egg-derived antigens induce a sustained and dominant Th2 response that mediates granuloma formation and liver fibrosis. In addition, the newly discovered Th17 cells also play a critical role in the hepatic immunopathology of schistosomiasis. Within the liver, Tregs are recruited to hepatic granulomas and exert an immunosuppressive role to limit the granulomatous inflammation and fibrosis. Moreover, recent studies have shown that Tfh and Th9 cells might also promote liver granulomas and fibrogenesis in the murine schistosomiasis. Thus, during infection, T-cell subsets undergo complicated cross-talk with antigen presenting cells that then defines their various roles in the local microenvironment for regulating the pathological progression of schistosomiasis. This current review summarizes a vast body of literature to elucidate the contribution of T lymphocytes and their associated cytokines in the immunopathology of schistosomiasis.

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Section: Tfh Promotes Liver Pathology Of Schistosomiasismentioning

confidence: 99%

Section: Tfh Promotes Liver Pathology Of Schistosomiasismentioning

confidence: 99%

Section: Summary and Concluding Commentsmentioning

confidence: 99%

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T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

et al. 2020

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“…The mechanisms of immunomodulation include IL-10, T regulatory cells, B cells, antibodies, and T cell anergy [12][13][14][15]. Besides, several studies have suggested that Th17 cells are involved in the pathogenesis of both S. mansoni and S. japonica [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Schistosoma Japonicuminfection in Treg-specific USP21 knock-out mice

Zhang

Zhang³

et al. 2020

Preprint

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34USP21, an E3 de-ubiquitin enzyme playing vital roles in 35 physiological activities, is important for Treg cells to maintain immune 36 homeostasis and control immune tolerance. To understand its diverse 37 functions and potential mechanism is essential for disease development. 38 We, using the USP21 gene-conditional knock-out mice model of 39 Schistosoma Japonicum infection, found more cercariae developed into 40 adults, and more eggs deposited in the liver in KO mice. However, 41 immunohistochemistry showed the degree and the area of egg 42 granuloma and liver fibrosis were both reduced. This suggested 43 knock-out USP21 did affect the immunoregulation between 44 schistosomes and the host. In KO mice the content of IFN-gamma and 45 IL-4, and the expression of anti-SEA IgG and anti-SWAP IgG both 46 increased in the liver, spleen and blood by flow 47 cytometry , while the content of IL-10, lL-17A, IL-23, IL-9 and the 48 expression of USP21 and anti-SEA IgM decreased. This indicated 49 USP21-knockout-Tregs promoted both Th1-type and Th2-type 50 immunity and inhibited other immunities during schistosomes infection, 51 which disordered the host immunity. This study revealed the 52 immunomodulatory of USP21 and preliminarily suggests it might be 53 essential to regulate the complex immune network between the host and 54 schistosomes. USP21 provides a new possible target for schistosomiasis 55 treatment in the future . 56 57 Author summary 58 Schistosomiasis is a common neglected tropical disease that 59 affects more than 230 million people worldwide. Therefore, the study on 60 the mechanism of immune interaction between schistosomas and the host 61 is not only helpful for the understanding of immune homeostasis, but also 62 helpful for the further development of the treatment of schistosomiasis. 63 Ubiquitin Specific Protease 21(USP21) has been shown to be involved in 64 the regulation of many biological processes, such as maintaining immune 65 homeostasis and regulating cell growth. Here, we observed that the 66 specific deletion of USP21 led to the decrease of mice's ability to resist 67 schistosomes infection and promoted the survival of schistosomes. It 68 was also proved that unstable regulatory T cells would produce 69 polarization phenomenon and promote differentiation to helper T cells, 70 which would lead to disorder of immune response in mice. However, this 71 process reduced the serious immune pathological damage caused by egg 72 granuloma. Our findings reveal that USP21 may be an important 73 molecule regulating immune interaction between Schistosoma japonicum 74 and the host. 75 76 Introduction 77 Schistosomiasis is an acute and chronic parasitic disease caused 78 by blood flukes (trematode worms) of the genus Schistosoma. According 79 to the WHO Report 2017, Schistosomiasis transmission was reported 80 from 78 countries, and at least 220.8 million people required preventive 81 treatment in 2017. The estimates of death due to Schistosomiasis 82 varies between 24 072 and 200 000 globally per yea...

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“…Tfh cells can promote antigen-specific B cell activation, germinal center formation and humoral responses [12,13]. In addition, Tfh cells are involved in the pathogenic process of some autoimmune diseases [14-16] and participate in defensing against parasite infection [17,18]. Indeed, increased frequency of Tfh cells is detected in rodent with S. japonicum infection and Tfh cells activated by ICOS + macrophages infiltrate into the liver and enhance the liver injury in mice infected with S. japonicum [19].…”

Section: Introductionmentioning

confidence: 99%

ICOS enhances follicular T helper responses and deteriorates the pathogenic process of liver in mice infected withSchistosoma japonicum

Wang

Song

Wang

et al. 2020

Preprint

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23 Background: Humoral immune responses play an important role in mediating liver 24 granulomatous inflammation and fibrosis in schistosomiasis. Follicular helper T (Tfh) cells 25 have a central role in mediating humoral immune responses. Generation of Tfh cells depends 26 on inducible T cell costimulator (ICOS) signaling, but the underlying molecular mechanisms 27 are incompletely understood in pathogenesis of schistosomiasis. 28 Methodology/Principal Findings: We used a strain of ICOS-transgenic (Tg) mice to 29 test the degrees of liver granulomatous inflammation and fibrosis, the frequency of splenic 30 Tfh cells and soluble egg antigen-specific cytokine responses longitudinally in mice 31following Schistosoma japonicum (S. japonicum) infection. In comparison with that in 32 wide-type (WT) mice, significantly severer liver granulomatous inflammation and fibrosis 33 and higher mortality were observed in ICOS-Tg mice. Significantly higher frequency of 34 splenic Tfh cells was accompanied by significantly higher levels of Bcl-6 and CXCR5 35 expression in the livers of ICOS-Tg mice. Furthermore, significantly higher levels of 36 SEA-specific IL-4, IL-6, IL-10, IL-13, IL-17A, IL-21 and TGF-β1 responses, but lower 37 levels of IFN-responses were detected in ICOS-Tg mice, which were abrogated by 38 treatment with ICOS blockers in vitro. In addition, significantly higher levels of serum 39 anti-SEA IgG were detected in ICOS-Tg mice. 40 Conclusions/Significance: The ICOS-related signaling may promote the pathogenesis 41 of murine schistosomiasis by polarizing Tfh cells, which may be immune check points for the 42 prevention and intervention of schistosomiasis.43 3 3 Author summary 44 Granulomatous inflammation and fibrosis in the liver are the major pathogenic 45 characteristics of schistosomiasis. ICOS is crucial for the development of Tfh cells, which are 46 the key modulators of B cell activation and humoral immunity. However, the underlying 47 molecular mechanisms are incompletely understood in pathogenesis of schistosomiasis. Here, 48 our results showed that the ICOS over-expression would significantly induce severer liver 49 inflammation and fibrosis, higher frequency of splenic Tfh, higher levels of anti-SEA IgG as 50 well as imbalanced SEA-specific cytokine responses in ICOS-Tg mice. The findings 51 suggested that ICOS signaling may promote the pathogenesis of murine schistosoma-related 52 liver inflammation and fibrosis by polarizing Tfh cells. Potentially, ICOS signaling and Tfh 53 cells may be immune check points for the prevention and intervention of schistosomiasis. 54 55 4 4 Introduction 56 S. japonicum infection remains a problem for human health in developing countries. 57 During the pathogenesis of schistosomiasis, S. japonicum infection-related egg deposition can 58 recruit inflammatory infiltrates and cause granulomatous inflammation and fibrosis in the 59 liver [1,2]. More importantly, continual pathogenic process of inflammation and fibrosis in 60 the liver usually impairs its function, even leadin...

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T follicular helper cells in patients with acute schistosomiasis

Cited by 16 publications

References 28 publications

T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

T Lymphocyte-Mediated Liver Immunopathology of Schistosomiasis

Schistosoma Japonicuminfection in Treg-specific USP21 knock-out mice

ICOS enhances follicular T helper responses and deteriorates the pathogenic process of liver in mice infected withSchistosoma japonicum

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