Critical Role of CD6 high CD4 + T Cells in Driving Th1/Th17 Cell Immune Responses and Mucosal Inflammation in IBD

Caiyun Ma, Wei Wu, Ritian Lin, Yadong Ge, Cui Zhang, Suofeng Sun, Yingzi Cong, Xiuling Li, Zhanju Liu

    Research output: Contribution to journalArticle

    3 Citations (Scopus)

    Abstract

    Background and Aims CD6 is a crucial regulator of T cell activation and is implicated in the pathogenesis of multiple autoimmune diseases. ALCAM is the first identified endogenous ligand of CD6. We sought to investigate potential roles of CD6 in regulating intestinal mucosal inflammation in inflammatory bowel disease [IBD]. Methods We analysed the expression of CD6 and ALCAM in the inflamed mucosa of IBD patients using qRT-PCR and immunohistochemistry. Phenotypic properties of CD6 low/â' and CD6 high CD4 + T cells were determined by flow cytometry, qRT-PCR, and ELISA. ALCAM Fc chimeric protein was used to evaluate the role of CD6-ALCAM engagement in regulating IBD CD4 + T cell activation and differentiation. Results Expression of CD6 and its ligand ALCAM was markedly increased in the inflamed mucosa of IBD patients compared with that in normal controls, and was significantly correlated with disease activity indices of IBD patients. Interestingly, CD6 high CD4 + T cells of IBD patients exhibited significantly higher pathogenicity compared with CD6 low/â CD4 + T cells, characterized by enhanced T cell activation and preferential Th1 and Th17 cell phenotypes, but a markedly decreased proportion of nTreg [CD25 high Foxp3 +, CD25 high CD127 low ] cells. Importantly, inclusion of ALCAM Fc chimeric protein significantly facilitated IBD CD4 + T cell, especially CD6 high CD4+ T cell, differentiation into Th1/Th17 cells compared with hIgG1 Fc-treated controls. Conclusions These data indicate that overexpression of CD6 and ALCAM in the inflamed mucosa of IBD patients accelerates intestinal mucosal immune responses via promoting CD4 + T cell proliferation and differentiation into Th1/Th17 cells. Thus, CD6 may serve as a novel therapeutic target for treatment of IBD.

    Original languageEnglish (US)
    Pages (from-to)510-524
    Number of pages15
    JournalJournal of Crohn's and Colitis
    Volume13
    Issue number4
    DOIs
    StatePublished - Mar 30 2019

    Fingerprint

    Activated-Leukocyte Cell Adhesion Molecule
    Th17 Cells
    Mucosal Immunity
    Th1 Cells
    Inflammatory Bowel Diseases
    Inflammation
    T-Lymphocytes
    Cell Differentiation
    Mucous Membrane
    Polymerase Chain Reaction
    Autoimmune Diseases
    Virulence
    Flow Cytometry
    Proteins
    Enzyme-Linked Immunosorbent Assay

    Keywords

    • ALCAM
    • CD4 + T cells
    • CD6
    • Inflammatory bowel diseases

    ASJC Scopus subject areas

    • Gastroenterology

    Cite this

    Critical Role of CD6 high CD4 + T Cells in Driving Th1/Th17 Cell Immune Responses and Mucosal Inflammation in IBD. / Ma, Caiyun; Wu, Wei; Lin, Ritian; Ge, Yadong; Zhang, Cui; Sun, Suofeng; Cong, Yingzi; Li, Xiuling; Liu, Zhanju.

    In: Journal of Crohn's and Colitis, Vol. 13, No. 4, 30.03.2019, p. 510-524.

    Research output: Contribution to journalArticle

    Ma, Caiyun ; Wu, Wei ; Lin, Ritian ; Ge, Yadong ; Zhang, Cui ; Sun, Suofeng ; Cong, Yingzi ; Li, Xiuling ; Liu, Zhanju. / Critical Role of CD6 high CD4 + T Cells in Driving Th1/Th17 Cell Immune Responses and Mucosal Inflammation in IBD. In: Journal of Crohn's and Colitis. 2019 ; Vol. 13, No. 4. pp. 510-524.
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    abstract = "Background and Aims CD6 is a crucial regulator of T cell activation and is implicated in the pathogenesis of multiple autoimmune diseases. ALCAM is the first identified endogenous ligand of CD6. We sought to investigate potential roles of CD6 in regulating intestinal mucosal inflammation in inflammatory bowel disease [IBD]. Methods We analysed the expression of CD6 and ALCAM in the inflamed mucosa of IBD patients using qRT-PCR and immunohistochemistry. Phenotypic properties of CD6 low/{\^a}' and CD6 high CD4 + T cells were determined by flow cytometry, qRT-PCR, and ELISA. ALCAM Fc chimeric protein was used to evaluate the role of CD6-ALCAM engagement in regulating IBD CD4 + T cell activation and differentiation. Results Expression of CD6 and its ligand ALCAM was markedly increased in the inflamed mucosa of IBD patients compared with that in normal controls, and was significantly correlated with disease activity indices of IBD patients. Interestingly, CD6 high CD4 + T cells of IBD patients exhibited significantly higher pathogenicity compared with CD6 low/{\^a} CD4 + T cells, characterized by enhanced T cell activation and preferential Th1 and Th17 cell phenotypes, but a markedly decreased proportion of nTreg [CD25 high Foxp3 +, CD25 high CD127 low ] cells. Importantly, inclusion of ALCAM Fc chimeric protein significantly facilitated IBD CD4 + T cell, especially CD6 high CD4+ T cell, differentiation into Th1/Th17 cells compared with hIgG1 Fc-treated controls. Conclusions These data indicate that overexpression of CD6 and ALCAM in the inflamed mucosa of IBD patients accelerates intestinal mucosal immune responses via promoting CD4 + T cell proliferation and differentiation into Th1/Th17 cells. Thus, CD6 may serve as a novel therapeutic target for treatment of IBD.",
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    author = "Caiyun Ma and Wei Wu and Ritian Lin and Yadong Ge and Cui Zhang and Suofeng Sun and Yingzi Cong and Xiuling Li and Zhanju Liu",
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    T1 - Critical Role of CD6 high CD4 + T Cells in Driving Th1/Th17 Cell Immune Responses and Mucosal Inflammation in IBD

    AU - Ma, Caiyun

    AU - Wu, Wei

    AU - Lin, Ritian

    AU - Ge, Yadong

    AU - Zhang, Cui

    AU - Sun, Suofeng

    AU - Cong, Yingzi

    AU - Li, Xiuling

    AU - Liu, Zhanju

    PY - 2019/3/30

    Y1 - 2019/3/30

    N2 - Background and Aims CD6 is a crucial regulator of T cell activation and is implicated in the pathogenesis of multiple autoimmune diseases. ALCAM is the first identified endogenous ligand of CD6. We sought to investigate potential roles of CD6 in regulating intestinal mucosal inflammation in inflammatory bowel disease [IBD]. Methods We analysed the expression of CD6 and ALCAM in the inflamed mucosa of IBD patients using qRT-PCR and immunohistochemistry. Phenotypic properties of CD6 low/â' and CD6 high CD4 + T cells were determined by flow cytometry, qRT-PCR, and ELISA. ALCAM Fc chimeric protein was used to evaluate the role of CD6-ALCAM engagement in regulating IBD CD4 + T cell activation and differentiation. Results Expression of CD6 and its ligand ALCAM was markedly increased in the inflamed mucosa of IBD patients compared with that in normal controls, and was significantly correlated with disease activity indices of IBD patients. Interestingly, CD6 high CD4 + T cells of IBD patients exhibited significantly higher pathogenicity compared with CD6 low/â CD4 + T cells, characterized by enhanced T cell activation and preferential Th1 and Th17 cell phenotypes, but a markedly decreased proportion of nTreg [CD25 high Foxp3 +, CD25 high CD127 low ] cells. Importantly, inclusion of ALCAM Fc chimeric protein significantly facilitated IBD CD4 + T cell, especially CD6 high CD4+ T cell, differentiation into Th1/Th17 cells compared with hIgG1 Fc-treated controls. Conclusions These data indicate that overexpression of CD6 and ALCAM in the inflamed mucosa of IBD patients accelerates intestinal mucosal immune responses via promoting CD4 + T cell proliferation and differentiation into Th1/Th17 cells. Thus, CD6 may serve as a novel therapeutic target for treatment of IBD.

    AB - Background and Aims CD6 is a crucial regulator of T cell activation and is implicated in the pathogenesis of multiple autoimmune diseases. ALCAM is the first identified endogenous ligand of CD6. We sought to investigate potential roles of CD6 in regulating intestinal mucosal inflammation in inflammatory bowel disease [IBD]. Methods We analysed the expression of CD6 and ALCAM in the inflamed mucosa of IBD patients using qRT-PCR and immunohistochemistry. Phenotypic properties of CD6 low/â' and CD6 high CD4 + T cells were determined by flow cytometry, qRT-PCR, and ELISA. ALCAM Fc chimeric protein was used to evaluate the role of CD6-ALCAM engagement in regulating IBD CD4 + T cell activation and differentiation. Results Expression of CD6 and its ligand ALCAM was markedly increased in the inflamed mucosa of IBD patients compared with that in normal controls, and was significantly correlated with disease activity indices of IBD patients. Interestingly, CD6 high CD4 + T cells of IBD patients exhibited significantly higher pathogenicity compared with CD6 low/â CD4 + T cells, characterized by enhanced T cell activation and preferential Th1 and Th17 cell phenotypes, but a markedly decreased proportion of nTreg [CD25 high Foxp3 +, CD25 high CD127 low ] cells. Importantly, inclusion of ALCAM Fc chimeric protein significantly facilitated IBD CD4 + T cell, especially CD6 high CD4+ T cell, differentiation into Th1/Th17 cells compared with hIgG1 Fc-treated controls. Conclusions These data indicate that overexpression of CD6 and ALCAM in the inflamed mucosa of IBD patients accelerates intestinal mucosal immune responses via promoting CD4 + T cell proliferation and differentiation into Th1/Th17 cells. Thus, CD6 may serve as a novel therapeutic target for treatment of IBD.

    KW - ALCAM

    KW - CD4 + T cells

    KW - CD6

    KW - Inflammatory bowel diseases

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    U2 - 10.1093/ecco-jcc/jjy179

    DO - 10.1093/ecco-jcc/jjy179

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