lncRNA028466 regulates Th1/Th2 cytokine expression and associates with Echinococcus granulosus antigen P29 immunity

Abstract Background Cystic echinococcosis (CE) is a parasitic disease that is caused by Echinococcus granulosus (Eg). The recombinant Echinococcus granulosus antigen P29 (rEg.P29) was shown to confer effective immunity to sheep and mice during E. granulosus secondary infection in our previous study. In this study, we sought to investigate the ability of long noncoding RNA 028466 (lncRNA028466) as a regulator for the protective immunity mediated by rEg.P29 vaccination and to study the effects of lncRNA028466 on CD4+T cell differentiation in mice spleen. Methods Female BALB/c mice were divided into two groups and were vaccinated subcutaneously with rEg.P29 antigen and PBS as a control (12 mice each group). Following prime-boost vaccination, CD4+T, CD8+T, and B cells from the spleen were isolated by flow cytometry. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of lncRNA028466 in these three kinds of cells. Then, lncRNA028466 was overexpressed and knocked down in naive CD4+T cells, and Th1 and Th2 cytokine expression was detected. qRT-PCR, western blot, and ELISA were performed to evaluate the production of IFN-γ, IL-2, IL-4, and IL-10, and flow cytometry was performed to detect the differentiation of Th1 and Th2 subgroups. Results lncRNA028466 was significantly decreased after the second week of immunization with rEg.P29 antigen. The proportion of CD4+ T cells was increased after rEg.P29 immunization. Overexpression of lncRNA028466 facilitated the production of IL-4, IL-10 and suppressed the production of IFN-γ, IL-2. Furthermore, after transfection with siRNA028466, IL-2 production was facilitated and IL-10 production was suppressed in naive CD4+ T cells. Conclusions Immunization with rEg.P29 downregulated the expression of lncRNA028466, which was related to a higher Th1 immune response and a lower Th2 immune response. Our results suggest that lncRNA028466 may be involved in rEg.P29-mediated immune response by regulating cytokine expression of Th1 and Th2.

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lncRNA028466 Regulates Th1/Th2 Cytokines Expression and Associated with Echinococcus Granulosus Antigen P29 Immunity

10.21203/rs.3.rs-245370/v1 ◽

2021 ◽

Author(s):

Chan Wang ◽

Songhao Yang ◽

Nan Niu ◽

Jia Tao ◽

Xiancai Du ◽

...

Keyword(s):

Flow Cytometry ◽

Immune Response ◽

T Cells ◽

Mrna Expression ◽

Echinococcus Granulosus ◽

Noncoding Rna ◽

Th2 Cytokines ◽

Qrt Pcr ◽

Ifn Γ ◽

Th1 And Th2

Abstract Background: Cystic echinococcosis (CE) is a parasite disease that was caused by Echinococcus granulosus (Eg). The recombinant Echinococcus granulosus antigen P29 (rEg.P29) has been shown to conferred effective immunity to sheep and mice during Echinococcus granulosus secondary infection in our previous study. In our study, we strove to research the ability of Long noncoding RNA 028466 (lncRNA028466) as a regulator for the protective immunity mediated by rEg.P29 vaccination and studied the effects of lncRNA028466 on CD4+T cells differentiation in mice spleen.Methods: Female BALB/c mice were divided into two groups and were vaccinated subcutaneously with rEg.P29 antigen and PBS as a control (12 mice each group). Following prime-boost vaccination, CD4+T, CD8+T，and B cells from the spleen were isolated by flow cytometry. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of lncRNA028466 in these three kinds of cells. Then, lncRNA028466 was over-expressed and knock-downed. Furthermore, were d by qRT-PCR and ELISA were performed to evaluate the production of IFN-γ, IL-2, IL-4, and IL-10, as well as was flow cytometry was performed to detect the differentiation of Th1 and Th2 subgroups. Results: lncRNA028466 was significantly decreased after the second-week of immunization with rEg.P29 antigen. The proportion of CD4+T cells was increased after rEg.P29 immunization. Subsequent overexpression and knockdown of lncRNA028466 in naive CD4+T cells were performed to detect changes in Th1 and Th2 cytokines expression. Overexpression of lncRNA028466 facilitated the production of IL-4, IL-10 and suppressed the production of IFN-γ, IL-2. Furthermore, after transfection with siRNA028466, IL-2 production was facilitated and IL-10 production was suppressed in naive CD4+T cells.Conclusions: Immunization with rEg.P29 down-regulated the expression of lncRNA028466, which was related to a higher Th1 immune response, a higher Th2 immune response with lncRNA028466 overexpression, a higher IL-2 mRNA expression, and a lower IL-10 mRNA expression with lncRNA028466 knockdown. Our results suggest that lncRNA028466 may be involved in rEg.P29-mediated immune response by regulating cytokines expression of Th1 and Th2.

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Cutaneous Leishmaniasis in Naturally Infected Dogs is Associated with a T Helper-2-biased Immune Response

Veterinary Pathology ◽

10.1354/vp.42-2-166 ◽

2005 ◽

Vol 42 (2) ◽

pp. 166-175 ◽

Cited By ~ 36

Author(s):

C. Brachelente ◽

N. Müller ◽

M. G. Doherr ◽

U. Sattler ◽

M. Welle

Keyword(s):

Immune Response ◽

Parasite Burden ◽

Skin Lesions ◽

Cytokine Expression ◽

T Helper ◽

T Helper 2 ◽

Th2 Cytokine ◽

Tnf Α ◽

Skin Biopsies ◽

Ifn Γ

Skin lesions are a frequent manifestation of Leishmania infantum infections in Mediterranean countries. This study demonstrates by real-time reverse transcriptase-polymerase chain reaction the local cytokine response in skin biopsies from Leishmania-infected dogs ( n = 10). As controls, we investigated skin biopsies from healthy ( n = 10) and fleabite hypersensitive dogs (n = 10). We established a quantitative PCR to determine the parasite burden in biopsies. The objective was to elucidate whether a correlation exists between parasite number, histologic response, and T helper-1 (TH1)/T helper-2 (TH2) cytokine expression in lesional skin of naturally infected dogs. In Leishmania-infected dogs, interleukin-4 (IL-4), tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) messenger RNA production was significantly higher than controls. Furthermore, dogs with a high Leishmania burden had a significantly higher IL-4 expression, whereas no difference was noted with regard to expression of other cytokines. By comparing the pattern of inflammation and cytokine expression, a clear trend became evident in that levels of IL-4, TNF-α, and IFN-γ were elevated in biopsies with a periadnexal nodular pattern and in biopsies where the severity of the periadnexal infiltrate was equal to the perivascular to interstitial infiltrate. Expression of IL-4, IL-13, and TNF-α was slightly increased in biopsies where plasma cells prevailed on lymphocytes, whereas expression of IFN-γ was moderately higher when lymphocytes were predominating. In summary, the present study demonstrates that the local immune response in naturally occurring leishmaniasis includes TH1 as well as TH2 cytokine subsets. Furthermore, respective data suggest that increased expression of the TH2-type cytokine IL-4 is associated with both severe clinical signs and a high parasite burden in the skin lesions.

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LncRNA-ENST00000421645 promotes T cells to secrete IFN-γ by sponging PCM-1 in neurosyphilis

Epigenomics ◽

10.2217/epi-2021-0163 ◽

2021 ◽

Author(s):

Wen-Na Liu ◽

Kai-Xuan Wu ◽

Xiao-Tong Wang ◽

Li-Rong Lin ◽

Man-Li Tong ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Peripheral Blood ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Chip Assay ◽

Rna Immunoprecipitation ◽

Ifn Γ ◽

Significant Expression

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA- ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA- ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA- ENST00000421645. Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA- ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA- ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.

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MiR-374b-5p Regulates T Cell Differentiation and Is Associated with rEg.P29 Immunity

BioMed Research International ◽

10.1155/2020/8024763 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Dongjie Li ◽

Xiancai Du ◽

Mingxing Zhu ◽

Songhao Yang ◽

Wei Zhao

Keyword(s):

Flow Cytometry ◽

Immune Response ◽

T Cells ◽

Cell Differentiation ◽

Echinococcus Granulosus ◽

Secondary Infection ◽

T Cell Differentiation ◽

Mrna Levels ◽

Th17 Differentiation ◽

Th1 Immune Response

Cystic echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus (Eg) infection. Our previous study confirmed that recombinant Eg.P29 (rEg.P29) could protect against echinococcus granulosus secondary infection in sheep and mice. The aim of the study was to investigate the association between immunoprotection of rEg.P29 vaccine and mmu-miR-374b-5p (miR-374b-5p) and study the immunity influence of miR-374b-5p on CD4+ T cells in mice spleen. MiR-374b-5p level was significantly increased after the second-week and the fourth week of vaccination with rEg.P29. Overexpression of miR-374b-5p increased IFN-γ, IL-2, IL-17A mRNA levels and decreased IL-10 mRNA levels in CD4+ T cells. Moreover, the inhibition of miR-374b-5p decreased IFN-γ and IL-17A and increased IL-10 mRNA levels in CD4+ T cells; this was further confirmed by the flow cytometry. The vaccination of rEg.P29 enhanced miR-374b-5p expression that was associated with a higher Th1 and Th17 immune response, a lower IL-10 mRNA production with miR-374b-5p overexpression, a lower Th1 immune response, and a higher IL-10 mRNA levels with miR-374b-5p inhibitions. To sum up, these data suggest that miR-374b-5p may participate in rEg.P29 immunity by regulating Th1 and Th17 differentiation.

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Correlation of IFNγ, CD107 and CD137 at the Single Cell Level Can Be Used To Monitor T Cell Responses in Patients after Immunotherapy.

Blood ◽

10.1182/blood.v110.11.2306.2306 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2306-2306

Author(s):

Debra K. Czerwinski ◽

Joshua D. Brody ◽

Ronald Levy

Keyword(s):

Flow Cytometry ◽

Immune Response ◽

T Cells ◽

T Cell ◽

B Cell ◽

Cd8 T Cells ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Cell Responses ◽

Ifn Γ

Abstract As immunotherapies become increasingly important in the treatment of various cancers, monitoring the immune response to reflect the efficacy of the therapy also becomes increasingly important. Previously, tumor antigen-specific humoral responses in patients receiving vaccines for low-grade follicular lymphoma (FL) correlated with clinical outcomes, including tumor regression, molecular remission, progression free survival (PFS) and overall survival (OS). By contrast, T cell immune responses have been difficult to validate. T cell proliferation assays, mostly, measure CD4 T cell responses; whereas, CD8 T cells may be the important effectors generated by immunotherapies. However, assays designed to measure CD8 T cells, i.e. chromium release CTL assays, and IFN-γ ELISPOT and intracellular flow cytometry assays, are difficult to make reproducible. To address this issue, PBL were obtained from FL patients, cryopreserved, and thawed, then used to design a standardized method for detection of intracellular IFN-γ by flow cytometry. The combined stimulus of soluble anti-CD3 and anti-CD28 antibodies provides a robust stimulation, typically about 5% of normal PBL CD8+ T cells respond. By using a panel of irradiated B cell lymphoma cell lines as stimulators, we demonstrated that, on average, 1 – 2% of these T cells were capable of mounting a response in this assay. Surprisingly, CD8+ PBL T cells from several patients with FL were more responsive to combined anti-CD3 and anti-CD28 stimulation as well as to allo-stimulation, 15 – 22% and 2 – 6%, respectively. This response was accompanied by surface expression of CD107, a surrogate marker for CTL degranulation, in the same population of cells as demonstrated by multi-color flow cytometry. Both the IFN-γ and the CD107 responses were inhibited by an anti-class I antibody, W6/32, suggesting a class I restricted T cell receptor-mediated response. Furthermore, at later time points, these T cells also up-regulated CD137 on their surface. This activation molecule is upregulated on CD8 T cells in response to specific antigen recognition and provides an anti-apoptotic signal to the cells. In conclusion, immune competency of CD8 T cells isolated from FL patients can be assessed through allo-stimulation by a panel of B cell lymphoma cell lines. More importantly, correlation by flow cytometry of 3 independent indicators of response (IFN-γ, CD107 and CD137) within single populations of cells to both allo-stimulation and to the specific target, may lead to better understanding of the role of T cells in the immune response. Ultimately, these responses will need to be validated with patient outcomes in clinical trials of vaccines in lymphoma.

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Evaluation of the Expression of CCR5 and CX3CR1 Receptors and Correlation with the Functionality of T Cells in Women infected with ZIKV during Pregnancy

Viruses ◽

10.3390/v13020191 ◽

2021 ◽

Vol 13 (2) ◽

pp. 191

Author(s):

Débora Familiar-Macedo ◽

Iury Amancio Paiva ◽

Jessica Badolato-Corrêa da Silva ◽

Fabiana Rabe de Carvalho ◽

Helver Gonçalves Dias ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Clinical Outcome ◽

Cell Responses ◽

Functional Assays ◽

Asymptomatic Children ◽

Cd107a Expression ◽

Congenital Zika Syndrome ◽

Ifn Γ

There have been reports of neurological abnormalities associated with the Zika virus (ZIKV), such as congenital Zika syndrome (CZS) in children born to mothers infected during pregnancy. We investigated how the immune response to ZIKV during pregnancy is primed and conduct a thorough evaluation of the inflammatory and cytotoxic profiles as well as the expression of CCR5 and CX3CR1. We compared the reactivity of T cells to ZIKV peptides in convalescent mothers infected during pregnancy. The child’s clinical outcome (i.e., born with or without CZS) was taken to be the variable. The cells were stimulated in vitro with ZIKV peptides and evaluated using the ELISPOT and flow cytometry assays. After in vitro stimulation with ZIKV peptides, we observed a tendency toward a higher Interferon gamma (IFN-γ)-producing T cell responses in mothers who had asymptomatic children and a higher CD107a expression in T cells in mothers who had children with CZS. We found a higher frequency of T cells expressing CD107a+ and co-expressing CX3CR1+CCR5+, which is much clearer in the T cells of mothers who had CZS children. We suggest that this differential profile influenced the clinical outcome of babies. These data need to be further investigated, including the evaluation of other ZIKV peptides and markers and functional assays.

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Checkpoint blockade accelerates a novel switch from an NKT-driven TNFα response toward a T cell driven IFN-γ response within the tumor microenvironment

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-002269 ◽

2021 ◽

Vol 9 (6) ◽

pp. e002269

Author(s):

Shota Aoyama ◽

Ryosuke Nakagawa ◽

Satoshi Nemoto ◽

Patricio Perez-Villarroel ◽

James J Mulé ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

T Cell ◽

Tumor Growth ◽

Ex Vivo ◽

T Cell Response ◽

Effector Function ◽

Checkpoint Blockade ◽

Necrosis Factor Alpha ◽

Ifn Γ

BackgroundThe temporal response to checkpoint blockade (CB) is incompletely understood. Here, we profiled the tumor infiltrating lymphocyte (TIL) landscape in response to combination checkpoint blockade at two distinct timepoints of solid tumor growth.MethodsC57BL/6 mice bearing subcutaneous MC38 tumors were treated with anti-PD-1 and/or anti-CTLA-4 antibodies. At 11 or 21 days, TIL phenotype and effector function were analyzed in excised tumor digests using high parameter flow cytometry. The contributions of major TIL populations toward overall response were then assessed using ex vivo cytotoxicity and in vivo tumor growth assays.ResultsThe distribution and effector function among 37 distinct TIL populations shifted dramatically between early and late MC38 growth. At 11 days, the immune response was dominated by Tumor necrosis factor alpha (TNFα)-producing NKT, representing over half of all TIL. These were accompanied by modest frequencies of natural killer (NK), CD4+, or CD8+ T cells, producing low levels of IFN-γ. At 21 days, NKT populations were reduced to a combined 20% of TIL, giving way to increased NK, CD4+, and CD8+ T cells, with increased IFN-γ production. Treatment with CB accelerated this switch. At day 11, CB reduced NKT to less than 20% of all TIL, downregulated TNFα across NKT and CD4+ T cell populations, increased CD4+ and CD8+ TIL frequencies, and significantly upregulated IFN-γ production. Degranulation was largely associated with NK and NKT TIL. Blockade of H-2kb and/or CD1d during ex vivo cytotoxicity assays revealed NKT has limited direct cytotoxicity against parent MC38. However, forced CD1d overexpression in MC38 cells significantly diminished tumor growth, suggesting NKT TIL exerts indirect control over MC38 growth.ConclusionsDespite an indirect benefit of early NKT activity, CB accelerates a switch from TNFα, NKT-driven immune response toward an IFN-γ driven CD4+/CD8+ T cell response in MC38 tumors. These results uncover a novel NKT/T cell switch that may be a key feature of CB response in CD1d+ tumors.

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The effect of Kefir on The Immune Response of Healthy Volunteers In Vitro

Journal of Agromedicine and Medical Sciences ◽

10.19184/ams.v3i2.5067 ◽

2017 ◽

Vol 3 (2) ◽

pp. 28

Author(s):

Desie Dwi Wisudanti

Keyword(s):

Immune Response ◽

T Cells ◽

Immune Responses ◽

Healthy Volunteers ◽

Cd8 T Cells ◽

Cd4 T Cells ◽

Fermented Milk ◽

Bioactive Components ◽

Ifn Γ

Kefir is a functional foodstuff of probiotics, made from fermented milk with kefir grains containing various types of beneficial bacteria and yeast. There have been many studies on the effects of oral kefir on the immune system, but few studies have shown the effect of bioactive components from kefir (peptides and exopolysaccharides/ kefiran), on immune responses. The purpose of this study was to prove the effect of kefir supernatant from milk goat on healthy immune volunteer response in vitro. The study was conducted on 15 healthy volunteers, then isolated PBMC from whole blood, then divided into 5 groups (K-, P1, P2, P3 and P4) before culture was done for 4 days. The harvested cells from culture were examined for the percentage of CD4+ T cells, CD8+ T cells, IFN-γ, IL-4 using flowsitometry and IL-2 levels, IL-10 using the ELISA method. The results obtained that kefir do not affect the percentage of CD4+ T cells and CD8+ T cells. The higher the concentration of kefir given, the higher levels of secreted IFN- γ and IL-4, but a decrease in IL-2 levels. Significant enhancement occurred at levels of IL-10 culture PBMC given kefir with various concentrations (p <0.01), especially at concentrations of 1%. These results also show the important effects of kefir bioactive components on immune responses. The conclusion of this study is that kefir can improve the immune response, through stimulation of IL-10 secretion in vitro.

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Bovine Immune Response to Vaccination and Infection with Leptospira borgpetersenii Serovar Hardjo

mSphere ◽

10.1128/msphere.00988-20 ◽

2021 ◽

Vol 6 (2) ◽

Author(s):

Jennifer H. Wilson-Welder ◽

David P. Alt ◽

Jarlath E. Nally ◽

Steven C. Olsen

Keyword(s):

Immune Response ◽

T Cells ◽

Lymph Nodes ◽

Γδ T Cells ◽

Regional Lymph Nodes ◽

Content Type ◽

Oil Emulsion ◽

Leptospira Borgpetersenii ◽

Ifn Γ ◽

Experimental Challenge

ABSTRACT This study examined the humoral and cellular response of cattle vaccinated with two commercial leptospiral vaccines, Leptavoid and Spirovac, and a novel bacterin vaccine using Seppic Montanide oil emulsion adjuvant. Vaccination was followed by experimental challenge. All vaccinated cattle were protected from colonization of the kidney and shedding of Leptospira in urine, as detected by culture and immunofluorescence assay. Agglutinating antibody titers were detected in vaccinated cattle at 4 weeks following vaccination, with small anamnestic response detected following experimental challenge. Only animals vaccinated with the oil emulsion-adjuvanted bacterin produced significant IgG2 titers following vaccination, and nonvaccinated animals produced serum IgA titers after experimental challenge. CD4+ and γδ T cells from vaccinated cattle proliferated when cultured with antigen ex vivo. Cellular responses included a marked proliferation of γδ T cells immediately following experimental challenge in vaccinated cattle and release of gamma interferon (IFN-γ), interleukin 17a (IL-17a), and IL-12p40 from stimulated cells. Proliferative and cytokine responses were found not just in peripheral mononuclear cells but also in lymphocytes isolated from renal lymph nodes at 10 weeks following experimental challenge. Overall, effects of leptospirosis vaccination and infection were subtle, resulting in only modest activation of CD4+ and γδ T cells. The use of Seppic Montanide oil emulsion adjuvants may shorten the initiation of response to vaccination, which could be useful during outbreaks or in areas where leptospirosis is endemic. IMPORTANCE Leptospirosis is an underdiagnosed, underreported zoonotic disease of which domestic livestock can be carriers. As a reservoir host for Leptospira borgpetersenii serovar Hardjo, cattle may present with reproductive issues, including abortion, birth of weak or infected calves, or failure to breed. Despite years of study and the availability of commercial vaccines, detailed analysis of the bovine immune response to vaccination and Leptospira challenge is lacking. This study evaluated immunologic responses to two efficacious commercial vaccines and a novel bacterin vaccine using an adjuvant chosen for enhanced cellular immune responses. Antigen-specific responsive CD4 and γδ T cells were detected following vaccination and were associated with release of inflammatory cytokines IFN-γ and IL-17a after stimulation. CD4 and γδ cells increased in the first week after infection and, combined with serum antibody, may play a role in clearance of bacteria from the blood and resident tissues. Additionally, these antigen-reactive T cells were found in the regional lymph nodes following infection, indicating that memory responses may not be circulating but are still present in regional lymph nodes. The information gained in this study expands knowledge of bovine immune response to leptospirosis vaccines and infection. The use of oil emulsion adjuvants may enhance early immune responses to leptospiral bacterins, which could be useful in outbreaks or situations where leptospirosis is endemic.

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CXCL12-CXCR4-Mediated Chemotaxis Supports Accumulation of Mucosal-Associated Invariant T Cells Into the Liver of Patients With PBC

Frontiers in Immunology ◽

10.3389/fimmu.2021.578548 ◽

2021 ◽

Vol 12 ◽

Author(s):

Zhilei Chen ◽

Suying Liu ◽

Chengmei He ◽

Jinlei Sun ◽

Li Wang ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Cytokine Production ◽

Immunofluorescence Staining ◽

Primary Biliary Cholangitis ◽

Hepatic Hemangioma ◽

Cxcr4 Antagonist ◽

Mait Cells ◽

Ifn Γ ◽

Invariant T Cells

Objectives: To explore the potential role of CD3+CD8+CD161high TCRVα7.2+ mucosal-associated invariant T (MAIT) cells in the pathogenesis of primary biliary cholangitis (PBC).Methods: We enrolled 55 patients with PBC, 69 healthy controls (HCs), and 8 patients with hepatic hemangioma. Circulating MAIT cells and their chemokine receptor profiles and cytokine production were quantified using flow cytometry. Liver-resident MAIT cells were examined by immunofluorescence staining. CXCL12-mediated chemotaxis of MAIT cells was measured using a transwell migration assay. Plasma interleukin (IL)-18 was measured using ELISA, and cytokine production in IL-18-stimulated MAIT cells was detected using flow cytometry.Result: Peripheral MAIT cells were found to be significantly lower in patients with PBC (3.0 ± 3.2% vs. 9.4 ± 8.0%, p < 0.01) and negatively correlated with alkaline phosphatase (ALP) levels (r = −0.3209, p < 0.05). Liver immunofluorescence staining suggested that MAIT cells might accumulate in PBC liver. MAIT cells from patients with PBC expressed higher levels of CXCR4 (84.8 ± 18.0% vs. 58.7 ± 11.4%, p < 0.01), and the expression of CXCL12 was higher in PBC liver. CXCL12 promoted MAIT cell chemotaxis (70.4 ± 6.8% vs. 52.2 ± 3.5%, p < 0.01), which was attenuated by CXCR4 antagonist. MAIT cells from PBC produced significantly more interferon-γ (IFN-γ) (88.3 ± 4.2% vs. 64.2 ± 10.1%, p < 0.01), tumor necrosis factor-α (TNF-α) (93.0 ± 1.1% vs. 80.1 ± 5.3%, p < 0.01), Granzyme B (89.3 ± 3.3% vs. 72.1 ± 7.0%, p < 0.01), and perforin (46.8 ± 6.6% vs. 34.8 ± 7.7%, p < 0.05). MAIT cells from PBC expressed higher levels of IL18-Rα (83.8 ± 10.2% vs. 58.3 ± 8.7%, p < 0.01). Plasma IL-18 was more abundant in patients with PBC (286.8 ± 75.7 pg/ml vs. 132.9 ± 78.1 pg/ml, p < 0.01). IL-18 promoted IFN-γ production in MAIT cells (74.9 ± 6.6% vs. 54.7 ± 6.7%, p < 0.01), which was partially attenuated by blocking IL-18R (68.6 ± 8.3% vs. 43.5 ± 4.2%, p < 0.01).Conclusion: Mucosal-associated invariant T cells from patients with PBC accumulated in the liver via CXCL12-CXCR4-mediated chemotaxis, produced pro-inflammatory cytokines, and contributed to portal inflammation, which was potentially mediated by elevated IL-18. Targeting MAIT cells might be a therapeutic approach for PBC.

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