Interleukin-17(IL-17),IL-21,IL-22 and IL-23 can be grouped as T helper 17(Th17)-related cytokines because they are either produced by Th17/Th22 cells or involved in their development.Here,we review Th17-related cytoki...Interleukin-17(IL-17),IL-21,IL-22 and IL-23 can be grouped as T helper 17(Th17)-related cytokines because they are either produced by Th17/Th22 cells or involved in their development.Here,we review Th17-related cytokines/Th17-like cells,networks/signals and their roles in immune responses or immunity against Mycobacterium tuberculosis(Mtb)infection.Published studies suggest that Th17-related cytokine pathways may be manipulated by Mtb microorganisms for their survival benefits in primary tuberculosis(TB).In addition,there is evidence that immune responses of the signal transducer and activator of transcription 3(STAT3)signal pathway and Th17-like T-cell subsets are dysregulated or destroyed in patients with TB.Furthermore,Mtb infection can impact upstream cytokines in the STAT3 pathway of Th17-like responses.Based on these findings,we discuss the need for future studies and the rationale for targeting Th17-related cytokines/signals as a potential adjunctive treatment.展开更多
Objective:To investigate the detection of Th17/Treg cell-related factors in patients with gestational diabetes mellitus(GDM)and its clinical significance.Methods:In this study,a retrospective cohort research method wa...Objective:To investigate the detection of Th17/Treg cell-related factors in patients with gestational diabetes mellitus(GDM)and its clinical significance.Methods:In this study,a retrospective cohort research method was used to collect the clinical data of 42 patients who were hospitalized in the Affiliated Hospital of Hebei University and received the diagnosis of GDM from January 2018 to December 2022,as well as 42 patients with normal pregnancies during the same period.The Th17/Treg expression levels and metabolism-related indexes in the peripheral blood of patients were detected by radioimmunoassay.Results:The relative expression of Th17 in the serum of patients in the GDM group was significantly higher than that of the control group,and the level of Treg was significantly lower than that of the control group(P<0.05);the levels of FBG,FINS,2hBG,TC,TG and HOMA-IR of the patients in the GDM group were significantly higher than that of the control group,and the level of HOMA-βwas significantly lower than that of the control group(P<0.05).Conclusion:The imbalance of the Th17/Treg cell ratio in patients with GDM may be related to their disease progression and prognosis,providing new ideas and strategies for the clinical treatment of GDM.展开更多
BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further inf...BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.展开更多
We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOM...We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOMP) isolated from <em>C</em>. <em>muridarum</em> elementary bodies (EBs) and recombinant PmpD and PmpG proteins were adjuvanted with Monophosphoryl lipid A (MPLA), with either lipid nanoparticles (LNPs) or the cationic lipid dimethyldioctadecylammonium bromide (DDA). Antibody titers to <em>C</em>. <em>muridarum</em> nMOMP, and EBs were evaluated by ELISA, and T-cell responses were analyzed by intracellular cytokine staining (ICS). Protection from challenge was determined by qPCR. Vaccine immunized mice showed significantly higher antibody titers to nMOMP (P < 0.001) and <em>C</em>. <em>muridarum</em> EBs (P < 0.001), when compared to the adjuvant alone group. Antibody titers in vaccine groups with Monophosphoryl lipid A (MPLA) + LNP were higher as compared to the MPLA + DDA group (P < 0.001) except for (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + DDA) vs (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + LNP) for both <em>C</em>. <em>muridarum</em> EBs and PmpG. ICS analysis showed more robust CD4 + T-cell responses (IFN-<em>γ</em>/IL-2/TNF-a) in the DDA and LNP groups compared to the adjuvant alone group. The DDA + MPLA gave robust Th17 responses in comparison to MPLA and LNP group. Mice immunized with <em>Chlamydia</em> antigens also showed protection from <em>C</em>. <em>muridarum</em> challenge, by reduction in bacterial shedding for all groups (P < 0.003) compared to shedding from the adjuvant control. Both vaccine formulations generated robust immunological responses, and both were protective by reducing bacterial shedding after challenge. This data indicates equal protection can be achieved without the induction of Th17 responses.展开更多
Objective:To investigate the Effect of saikosaponin A on Treg and Th17 immune balance in depressive rats.Methods:The rat depression model was established with reference to the Katz method,and the rats were randomly di...Objective:To investigate the Effect of saikosaponin A on Treg and Th17 immune balance in depressive rats.Methods:The rat depression model was established with reference to the Katz method,and the rats were randomly divided into control group,model group,western medicine group,and saikosaponin A group.The western medicine group was given 1.2 mg/kg/d of fluoxetine,and the saikosaponin A group was given 25 mg/kg/d of saikosaponin A,while the control group and model group were given the same volume of normal saline.The evaluation of depression in Rats was analyzed by Openfield-test and sugar water preference test.Flow cytometry was used to detect the expression of Th17 and Treg cells.And the expression of IL-17,IL-23,TNF-α,IL-10,TGF-βwere detected by enzyme-linked immunosorbent assay(ELISA).Results:Compared with the control group,the horizontal exercise score,vertical exercise score,and sugar preference of the model group decreased significantly(P<0.05).Compared with the model group,the above indicators were significantly increased in the western medicine group and saikosaponin A group(P<0.05).Flow cytometry showed that compared with the control group,the Th17 cells,Th17/Treg cell ratio in model group increased significantly,whereas the Treg cells decreased significantly(P<0.05).Compared with the model group,The Th17 cells and Th17/Treg ratio in western medicine group and saikosaponin A group decreased,while the Treg cells increased significantly(P<0.05).ELISA showed that compared with control group,the serum levels of IL-17,IL-23 and TNF-αin model group increased,while the levels of IL-10 and TGF-βdecreased(P<0.05).Compared with model group,the levels of IL-17,IL-23 and TNF-αdecreased,while the levels of IL-10 and TGF-βincreased in western medicine group and saikosaponin A group(P<0.05).Conclusion:Saikosaponin A can reduce the degree of depression by regulating the imbalance of Th17/Treg cells and the secretion of inflammatory cytokines in depressed rats.展开更多
AIM: To assess helper T(Th) lymphocyte subset balance in patients with Vogt-Koyanagi-Harada(VKH) disease. METHODS: Sixty-eight active VKH patients and seventytwo inactive VKH patients were included in this study. One ...AIM: To assess helper T(Th) lymphocyte subset balance in patients with Vogt-Koyanagi-Harada(VKH) disease. METHODS: Sixty-eight active VKH patients and seventytwo inactive VKH patients were included in this study. One hundred healthy individuals served as controls. Peripheral blood was obtained from VKH patients and healthy controls. Th lymphocyte subsets were analyzed by flow cytometry. Plasma concentration of interleukin(IL)-17, IL-10, transforming growth factor(TGF)-β, IL-23 and IL-6 was examined by enzyme-linked immunosorbent assay(ELISA). RESULTS: VKH patients with active uveitis had significantly higher percentages of both Th1 and Th17 cells and lower percentages of regulatory T(Treg) cells as compared with inactive VKH patients and healthy controls. Th1/Th2 and Th17/Treg ratios were also significantly elevated in active VKH patients. The percentages of Th1, Th17 and Treg cells and the Th1/Th2, Th17/Treg ratio did not differ between inactive VKH patients and healthy controls. There was no difference concerning the percentage of Th2 cells among all the groups. VKH patients with active uveitis showed an elevated level of peripheral Th17 related cytokines levels(TGF-β, IL-6, IL-23, and IL-17) and a decreased level of Treg related cytokines(IL-10) compared with inactive VKH patients and healthy controls. Inactive VKH patients showed no differences in peripheral Th17 related cytokines(TGF-β, IL-6, IL-23, and IL-17) and Treg related cytokines(IL-10) levels compared with healthy controls. CONCLUSION: Th1 and Th17 cells are significantly increased and Treg cells significantly decreased in active VKH compared with inactive VKH or healthy controls. Therefore, Th lymphocyte subset analysis may serve as a disease biomarker for VKH.展开更多
Rheumatoid arthritis (RA) is associated with an HLA-DRB1-coded sequence motif called “shared epitope” (SE). To explore potential mechanisms of RA susceptibility, we analyze in vitro effect of peptides bearing differ...Rheumatoid arthritis (RA) is associated with an HLA-DRB1-coded sequence motif called “shared epitope” (SE). To explore potential mechanisms of RA susceptibility, we analyze in vitro effect of peptides bearing different HLA-DR4 sequences on human peripheral blood-derived cells. Three 15-mer peptides were used: 65-79*0401 (HLA-DRB1*04:01- coded sequence SE motif, QKRAA);65-79*0402 (HLA-DRB1*04:02-coded sequence SE-negative motif, DERAA);65-79*0403 (HLA-DRB1*04:03-coded sequence SE-negative motif, QRRAE). We found that CD4 TH17 cells are regulated by peptide treatment with gender bias. In male-derived T cells, all peptide treatments significantly reduced TH17 cell differentiation in vitro when compared to no peptide treatment, and to female samples. TH17 differentiation in samples not treated with peptides, either in the presence or absence of TH17-polarizing cytokines, was higher in males than in females;however, in unfractionated PBMC after treatment with TH17 polarizing cytokines, IL-17A-positive cells were more abundant in females than in males. In addition, SE-positive females showed a significantly higher percentage of IL-17A-positive cells compared to SE-negative females. In conclusion, donor’s SE status and gender may both influence TH17 immune polarization.展开更多
AIM: to investigate the effect of Bifidobacterium infantis (B. infantis) on the T cell subsets and in attenuating the severity of experimental colitis in mice.
Dear Editor,External cytokines produced by cells of the innate immune system induce the dif-ferentiation of CD4+T cells into helper T cell subsets with distinct functions and cytokine profiles.Apart from TH1 and TH2 c...Dear Editor,External cytokines produced by cells of the innate immune system induce the dif-ferentiation of CD4+T cells into helper T cell subsets with distinct functions and cytokine profiles.Apart from TH1 and TH2 cells a third subset of helper T cells has been described,which is characterized by increased expression of IL-17A,IL-17F,IL-21 and IL-22(TH17 cells).展开更多
Background::Recently,T-helper 17(Th17)cells have been proved to play an important role in promoting cervical cancer.But,till now,few study has been carried out to understand the involvement of these cells in efficacy ...Background::Recently,T-helper 17(Th17)cells have been proved to play an important role in promoting cervical cancer.But,till now,few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments.This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer(LACC)patients before and after concurrent chemoradiotherapy(cCRT)and to analyze the correlations between the alterations in Th17 cells and treatment efficacy.Methods::A prospective study with 49 LACC(International federation of gynecology and obstetrics[FIGO]stage IIB-IIIB)patients and 23 controls was conducted.Patients received the same cCRT schedule and were followed up for 3 years.Circulating Th17 cells(CD3+CD8-interleukin[IL]-17+T cells)and related cytokines IL-17,transforming growth factor-β(TGF-β),IL-10,IL-23,IL-6,and IL-22 were detected before and after cCRT.Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed.Kaplan-Meier analysis was used for overall survival(OS)and progression-free survival(PFS).Results::We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study.The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls,and it significantly decreased after cCRT(P<0.05).After cCRT,patients were divided into two groups based on the average of the Th17 cells declined.The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times.Compared with the control patients,LACC patients had higher IL-6,IL-10,IL-22,TGF-βlevels and a lower IL-23 level(P<0.05).After cCRT,IL-6,IL-10,IL-17,IL-23 level significantly increased and TGF-βlevel significantly decreased compared with the levels before cCRT(P<0.05).Conclusion::Circulating Th17 cells in the LACC patients(FIGO stage IIB-IIIB)were higher than those in the controls,but they generally decreased after cCRT.A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.展开更多
基金This work was supported by the following research grants:The National Key Research and Development Program of China(2016YFA0502204)the National Institutes of Health R01 grants(NIH R01 HL64560/OD015092/HL129887 to ZWC).
文摘Interleukin-17(IL-17),IL-21,IL-22 and IL-23 can be grouped as T helper 17(Th17)-related cytokines because they are either produced by Th17/Th22 cells or involved in their development.Here,we review Th17-related cytokines/Th17-like cells,networks/signals and their roles in immune responses or immunity against Mycobacterium tuberculosis(Mtb)infection.Published studies suggest that Th17-related cytokine pathways may be manipulated by Mtb microorganisms for their survival benefits in primary tuberculosis(TB).In addition,there is evidence that immune responses of the signal transducer and activator of transcription 3(STAT3)signal pathway and Th17-like T-cell subsets are dysregulated or destroyed in patients with TB.Furthermore,Mtb infection can impact upstream cytokines in the STAT3 pathway of Th17-like responses.Based on these findings,we discuss the need for future studies and the rationale for targeting Th17-related cytokines/signals as a potential adjunctive treatment.
基金Baoding Science and Technology Program Project(2041ZF295)Hebei University Medical Discipline Cultivation Program(2022B03)。
文摘Objective:To investigate the detection of Th17/Treg cell-related factors in patients with gestational diabetes mellitus(GDM)and its clinical significance.Methods:In this study,a retrospective cohort research method was used to collect the clinical data of 42 patients who were hospitalized in the Affiliated Hospital of Hebei University and received the diagnosis of GDM from January 2018 to December 2022,as well as 42 patients with normal pregnancies during the same period.The Th17/Treg expression levels and metabolism-related indexes in the peripheral blood of patients were detected by radioimmunoassay.Results:The relative expression of Th17 in the serum of patients in the GDM group was significantly higher than that of the control group,and the level of Treg was significantly lower than that of the control group(P<0.05);the levels of FBG,FINS,2hBG,TC,TG and HOMA-IR of the patients in the GDM group were significantly higher than that of the control group,and the level of HOMA-βwas significantly lower than that of the control group(P<0.05).Conclusion:The imbalance of the Th17/Treg cell ratio in patients with GDM may be related to their disease progression and prognosis,providing new ideas and strategies for the clinical treatment of GDM.
基金Supported by the Medical University of Sofia,No.22.2012-2013Trakia University of Stara Zagora,No.1.2016 and No.2.2017.
文摘BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.
文摘We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOMP) isolated from <em>C</em>. <em>muridarum</em> elementary bodies (EBs) and recombinant PmpD and PmpG proteins were adjuvanted with Monophosphoryl lipid A (MPLA), with either lipid nanoparticles (LNPs) or the cationic lipid dimethyldioctadecylammonium bromide (DDA). Antibody titers to <em>C</em>. <em>muridarum</em> nMOMP, and EBs were evaluated by ELISA, and T-cell responses were analyzed by intracellular cytokine staining (ICS). Protection from challenge was determined by qPCR. Vaccine immunized mice showed significantly higher antibody titers to nMOMP (P < 0.001) and <em>C</em>. <em>muridarum</em> EBs (P < 0.001), when compared to the adjuvant alone group. Antibody titers in vaccine groups with Monophosphoryl lipid A (MPLA) + LNP were higher as compared to the MPLA + DDA group (P < 0.001) except for (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + DDA) vs (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + LNP) for both <em>C</em>. <em>muridarum</em> EBs and PmpG. ICS analysis showed more robust CD4 + T-cell responses (IFN-<em>γ</em>/IL-2/TNF-a) in the DDA and LNP groups compared to the adjuvant alone group. The DDA + MPLA gave robust Th17 responses in comparison to MPLA and LNP group. Mice immunized with <em>Chlamydia</em> antigens also showed protection from <em>C</em>. <em>muridarum</em> challenge, by reduction in bacterial shedding for all groups (P < 0.003) compared to shedding from the adjuvant control. Both vaccine formulations generated robust immunological responses, and both were protective by reducing bacterial shedding after challenge. This data indicates equal protection can be achieved without the induction of Th17 responses.
基金Hebei Science and technology program 2017 Hebei key R&D plan big health service and biomedical special project(No.17277782D)
文摘Objective:To investigate the Effect of saikosaponin A on Treg and Th17 immune balance in depressive rats.Methods:The rat depression model was established with reference to the Katz method,and the rats were randomly divided into control group,model group,western medicine group,and saikosaponin A group.The western medicine group was given 1.2 mg/kg/d of fluoxetine,and the saikosaponin A group was given 25 mg/kg/d of saikosaponin A,while the control group and model group were given the same volume of normal saline.The evaluation of depression in Rats was analyzed by Openfield-test and sugar water preference test.Flow cytometry was used to detect the expression of Th17 and Treg cells.And the expression of IL-17,IL-23,TNF-α,IL-10,TGF-βwere detected by enzyme-linked immunosorbent assay(ELISA).Results:Compared with the control group,the horizontal exercise score,vertical exercise score,and sugar preference of the model group decreased significantly(P<0.05).Compared with the model group,the above indicators were significantly increased in the western medicine group and saikosaponin A group(P<0.05).Flow cytometry showed that compared with the control group,the Th17 cells,Th17/Treg cell ratio in model group increased significantly,whereas the Treg cells decreased significantly(P<0.05).Compared with the model group,The Th17 cells and Th17/Treg ratio in western medicine group and saikosaponin A group decreased,while the Treg cells increased significantly(P<0.05).ELISA showed that compared with control group,the serum levels of IL-17,IL-23 and TNF-αin model group increased,while the levels of IL-10 and TGF-βdecreased(P<0.05).Compared with model group,the levels of IL-17,IL-23 and TNF-αdecreased,while the levels of IL-10 and TGF-βincreased in western medicine group and saikosaponin A group(P<0.05).Conclusion:Saikosaponin A can reduce the degree of depression by regulating the imbalance of Th17/Treg cells and the secretion of inflammatory cytokines in depressed rats.
基金Supported by National Natural Science Foundation of China(No.30772013)Basic Research Program of Chongqing(No.cstc2015jcyjA10112)
文摘AIM: To assess helper T(Th) lymphocyte subset balance in patients with Vogt-Koyanagi-Harada(VKH) disease. METHODS: Sixty-eight active VKH patients and seventytwo inactive VKH patients were included in this study. One hundred healthy individuals served as controls. Peripheral blood was obtained from VKH patients and healthy controls. Th lymphocyte subsets were analyzed by flow cytometry. Plasma concentration of interleukin(IL)-17, IL-10, transforming growth factor(TGF)-β, IL-23 and IL-6 was examined by enzyme-linked immunosorbent assay(ELISA). RESULTS: VKH patients with active uveitis had significantly higher percentages of both Th1 and Th17 cells and lower percentages of regulatory T(Treg) cells as compared with inactive VKH patients and healthy controls. Th1/Th2 and Th17/Treg ratios were also significantly elevated in active VKH patients. The percentages of Th1, Th17 and Treg cells and the Th1/Th2, Th17/Treg ratio did not differ between inactive VKH patients and healthy controls. There was no difference concerning the percentage of Th2 cells among all the groups. VKH patients with active uveitis showed an elevated level of peripheral Th17 related cytokines levels(TGF-β, IL-6, IL-23, and IL-17) and a decreased level of Treg related cytokines(IL-10) compared with inactive VKH patients and healthy controls. Inactive VKH patients showed no differences in peripheral Th17 related cytokines(TGF-β, IL-6, IL-23, and IL-17) and Treg related cytokines(IL-10) levels compared with healthy controls. CONCLUSION: Th1 and Th17 cells are significantly increased and Treg cells significantly decreased in active VKH compared with inactive VKH or healthy controls. Therefore, Th lymphocyte subset analysis may serve as a disease biomarker for VKH.
文摘Rheumatoid arthritis (RA) is associated with an HLA-DRB1-coded sequence motif called “shared epitope” (SE). To explore potential mechanisms of RA susceptibility, we analyze in vitro effect of peptides bearing different HLA-DR4 sequences on human peripheral blood-derived cells. Three 15-mer peptides were used: 65-79*0401 (HLA-DRB1*04:01- coded sequence SE motif, QKRAA);65-79*0402 (HLA-DRB1*04:02-coded sequence SE-negative motif, DERAA);65-79*0403 (HLA-DRB1*04:03-coded sequence SE-negative motif, QRRAE). We found that CD4 TH17 cells are regulated by peptide treatment with gender bias. In male-derived T cells, all peptide treatments significantly reduced TH17 cell differentiation in vitro when compared to no peptide treatment, and to female samples. TH17 differentiation in samples not treated with peptides, either in the presence or absence of TH17-polarizing cytokines, was higher in males than in females;however, in unfractionated PBMC after treatment with TH17 polarizing cytokines, IL-17A-positive cells were more abundant in females than in males. In addition, SE-positive females showed a significantly higher percentage of IL-17A-positive cells compared to SE-negative females. In conclusion, donor’s SE status and gender may both influence TH17 immune polarization.
基金Supported by Guangzhou Baoxing Biotechnology Company
文摘AIM: to investigate the effect of Bifidobacterium infantis (B. infantis) on the T cell subsets and in attenuating the severity of experimental colitis in mice.
文摘Dear Editor,External cytokines produced by cells of the innate immune system induce the dif-ferentiation of CD4+T cells into helper T cell subsets with distinct functions and cytokine profiles.Apart from TH1 and TH2 cells a third subset of helper T cells has been described,which is characterized by increased expression of IL-17A,IL-17F,IL-21 and IL-22(TH17 cells).
基金the National Key Research and Development Program of China(No:2016YFC1302904)the National Natural Science Foundation of China(No:81572559)the Key Research Project of Shandong Province(No:2017CXGC1210).
文摘Background::Recently,T-helper 17(Th17)cells have been proved to play an important role in promoting cervical cancer.But,till now,few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments.This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer(LACC)patients before and after concurrent chemoradiotherapy(cCRT)and to analyze the correlations between the alterations in Th17 cells and treatment efficacy.Methods::A prospective study with 49 LACC(International federation of gynecology and obstetrics[FIGO]stage IIB-IIIB)patients and 23 controls was conducted.Patients received the same cCRT schedule and were followed up for 3 years.Circulating Th17 cells(CD3+CD8-interleukin[IL]-17+T cells)and related cytokines IL-17,transforming growth factor-β(TGF-β),IL-10,IL-23,IL-6,and IL-22 were detected before and after cCRT.Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed.Kaplan-Meier analysis was used for overall survival(OS)and progression-free survival(PFS).Results::We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study.The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls,and it significantly decreased after cCRT(P<0.05).After cCRT,patients were divided into two groups based on the average of the Th17 cells declined.The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times.Compared with the control patients,LACC patients had higher IL-6,IL-10,IL-22,TGF-βlevels and a lower IL-23 level(P<0.05).After cCRT,IL-6,IL-10,IL-17,IL-23 level significantly increased and TGF-βlevel significantly decreased compared with the levels before cCRT(P<0.05).Conclusion::Circulating Th17 cells in the LACC patients(FIGO stage IIB-IIIB)were higher than those in the controls,but they generally decreased after cCRT.A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.