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Follicular Helper CD4+ T Cells in Human Neuroautoimmune Diseases and Their Animal Models.

Fan X, Lin C, Han J, Jiang X, Zhu J, Jin T - Mediators Inflamm. (2015)

Bottom Line: TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21.It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells.This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun 130021, China.

ABSTRACT
Follicular helper CD4(+) T (TFH) cells play a fundamental role in humoral immunity deriving from their ability to provide help for germinal center (GC) formation, B cell differentiation into plasma cells and memory cells, and antibody production in secondary lymphoid tissues. TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells. A balance of TFH cell generation and function is critical for protective antibody response, whereas overactivation of TFH cells or overexpression of TFH-associated molecules may result in autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated molecules may be involved in the pathogenesis of neuroautoimmune diseases including multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG). This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models.

No MeSH data available.


Related in: MedlinePlus

Effector subsets of CD4+ T cells: ontogenic and major cytokines, and roles in diseases. Naive CD4+ T cells differentiate into diverse effector subsets dependent on stimulatory cytokines in the microenvironment upon activation by pathogens. These stimulatory cytokines induce transcription factors expression of these subsets. IL-12 induces T-bet in the case of Th1 cells, IL-4 induces GATA3 in the case of Th2 cells, TGF-β, IL-6, and IL-23 induce RORγt and RORα in the case of Th17 cells, TGF-β induces Foxp3 in the case of Treg cells, and IL-6 and IL-21 induce Bcl-6 in the case of TFH cells. Subsequently, different effector subsets produce distinct cytokines and acquire specialized effector function. Th1 cells produce IFN-γ associated with antiviral and antibacterial immunity and cell-mediated immunity, Th2 cells produce IL-4 associated with immunity to extracellular parasites, Th17 cells produce IL-17 associated with inflammation, fungal immunity, and protection at mucocutaneous sites, Treg cells produce TGF-β and IL-10 associated with regulation, tolerance, and immune suppression, and TFH cells produce IL-21 associated with providing help for B cell differentiation and antibody production. Bcl-6, B cell lymphoma 6; Foxp3, forkhead box p3; GATA-3, GATA-binding protein 3; IFN-γ, interferon-γ; IL-4, interleukin 4; IL-6, interleukin 6; IL-10, interleukin 10; IL-12, interleukin 12; IL-17, interleukin 17; IL-21, interleukin 21; IL-23, interleukin 23; RORγt, retinoid-related orphan receptor γt; RORα, retinoid-related orphan receptor α; T-bet, T-box transcription factor; TGF-β, transforming growth factor-β; TNF, tumour necrosis factor; Treg, T regulator.
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Related In: Results  -  Collection


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fig1: Effector subsets of CD4+ T cells: ontogenic and major cytokines, and roles in diseases. Naive CD4+ T cells differentiate into diverse effector subsets dependent on stimulatory cytokines in the microenvironment upon activation by pathogens. These stimulatory cytokines induce transcription factors expression of these subsets. IL-12 induces T-bet in the case of Th1 cells, IL-4 induces GATA3 in the case of Th2 cells, TGF-β, IL-6, and IL-23 induce RORγt and RORα in the case of Th17 cells, TGF-β induces Foxp3 in the case of Treg cells, and IL-6 and IL-21 induce Bcl-6 in the case of TFH cells. Subsequently, different effector subsets produce distinct cytokines and acquire specialized effector function. Th1 cells produce IFN-γ associated with antiviral and antibacterial immunity and cell-mediated immunity, Th2 cells produce IL-4 associated with immunity to extracellular parasites, Th17 cells produce IL-17 associated with inflammation, fungal immunity, and protection at mucocutaneous sites, Treg cells produce TGF-β and IL-10 associated with regulation, tolerance, and immune suppression, and TFH cells produce IL-21 associated with providing help for B cell differentiation and antibody production. Bcl-6, B cell lymphoma 6; Foxp3, forkhead box p3; GATA-3, GATA-binding protein 3; IFN-γ, interferon-γ; IL-4, interleukin 4; IL-6, interleukin 6; IL-10, interleukin 10; IL-12, interleukin 12; IL-17, interleukin 17; IL-21, interleukin 21; IL-23, interleukin 23; RORγt, retinoid-related orphan receptor γt; RORα, retinoid-related orphan receptor α; T-bet, T-box transcription factor; TGF-β, transforming growth factor-β; TNF, tumour necrosis factor; Treg, T regulator.

Mentions: CD4+ T helper (Th) cells play a critical role in adaptive immune response. After infection or vaccination, naive CD4+ T cells differentiate into diverse effector subsets of Th cells dependent on distinct cytokines and transcription factors [1–5] (Figure 1). These Th cell subsets possess respective effector function, for instance, the antiviral role of Th1 cells and the role in elimination of extracellular parasites of Th2 [2, 3] (Figure 1). Recently, follicular helper CD4+ T (TFH) cells, a specialized subset of CD4+ Th cells, have been identified as providing help for B cells in germinal center (GC) [6, 7]. GC is an important structure in B cell follicles of secondary lymphoid tissues, where B cells can differentiate into plasma cells and memory cells. TFH cells are distinguished from other Th cell subsets by anatomical location (germinal center), specialized expression of transcription factor B cell lymphoma 6 (Bcl-6), chemokine receptor CXC-chemokine receptor 5 (CXCR5), programmed death-1 (PD-1), CD40 ligand (CD40L), inducible costimulator (ICOS), SAP (signaling lymphocytic activation molecule associated protein), and secretion of interleukin 21 (IL-21) and interleukin 4 (IL-4) [8–10]. These TFH-associated molecules are vital for activation, differentiation, and survival of TFH cells and B cells [11]. In a word, TFH cells are pivotal to GC formation, providing help for affinity maturation, class switch recombination, and ultimate differentiation of B cells within GC [12]. The present review outlines the features of TFH cells and TFH-associated molecules in neuroautoimmune diseases, especially in multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG) as well as their animal models, experimental autoimmune encephalomyelitis (EAE), and experimental autoimmune myasthenia gravis (EAMG).


Follicular Helper CD4+ T Cells in Human Neuroautoimmune Diseases and Their Animal Models.

Fan X, Lin C, Han J, Jiang X, Zhu J, Jin T - Mediators Inflamm. (2015)

Effector subsets of CD4+ T cells: ontogenic and major cytokines, and roles in diseases. Naive CD4+ T cells differentiate into diverse effector subsets dependent on stimulatory cytokines in the microenvironment upon activation by pathogens. These stimulatory cytokines induce transcription factors expression of these subsets. IL-12 induces T-bet in the case of Th1 cells, IL-4 induces GATA3 in the case of Th2 cells, TGF-β, IL-6, and IL-23 induce RORγt and RORα in the case of Th17 cells, TGF-β induces Foxp3 in the case of Treg cells, and IL-6 and IL-21 induce Bcl-6 in the case of TFH cells. Subsequently, different effector subsets produce distinct cytokines and acquire specialized effector function. Th1 cells produce IFN-γ associated with antiviral and antibacterial immunity and cell-mediated immunity, Th2 cells produce IL-4 associated with immunity to extracellular parasites, Th17 cells produce IL-17 associated with inflammation, fungal immunity, and protection at mucocutaneous sites, Treg cells produce TGF-β and IL-10 associated with regulation, tolerance, and immune suppression, and TFH cells produce IL-21 associated with providing help for B cell differentiation and antibody production. Bcl-6, B cell lymphoma 6; Foxp3, forkhead box p3; GATA-3, GATA-binding protein 3; IFN-γ, interferon-γ; IL-4, interleukin 4; IL-6, interleukin 6; IL-10, interleukin 10; IL-12, interleukin 12; IL-17, interleukin 17; IL-21, interleukin 21; IL-23, interleukin 23; RORγt, retinoid-related orphan receptor γt; RORα, retinoid-related orphan receptor α; T-bet, T-box transcription factor; TGF-β, transforming growth factor-β; TNF, tumour necrosis factor; Treg, T regulator.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4537760&req=5

fig1: Effector subsets of CD4+ T cells: ontogenic and major cytokines, and roles in diseases. Naive CD4+ T cells differentiate into diverse effector subsets dependent on stimulatory cytokines in the microenvironment upon activation by pathogens. These stimulatory cytokines induce transcription factors expression of these subsets. IL-12 induces T-bet in the case of Th1 cells, IL-4 induces GATA3 in the case of Th2 cells, TGF-β, IL-6, and IL-23 induce RORγt and RORα in the case of Th17 cells, TGF-β induces Foxp3 in the case of Treg cells, and IL-6 and IL-21 induce Bcl-6 in the case of TFH cells. Subsequently, different effector subsets produce distinct cytokines and acquire specialized effector function. Th1 cells produce IFN-γ associated with antiviral and antibacterial immunity and cell-mediated immunity, Th2 cells produce IL-4 associated with immunity to extracellular parasites, Th17 cells produce IL-17 associated with inflammation, fungal immunity, and protection at mucocutaneous sites, Treg cells produce TGF-β and IL-10 associated with regulation, tolerance, and immune suppression, and TFH cells produce IL-21 associated with providing help for B cell differentiation and antibody production. Bcl-6, B cell lymphoma 6; Foxp3, forkhead box p3; GATA-3, GATA-binding protein 3; IFN-γ, interferon-γ; IL-4, interleukin 4; IL-6, interleukin 6; IL-10, interleukin 10; IL-12, interleukin 12; IL-17, interleukin 17; IL-21, interleukin 21; IL-23, interleukin 23; RORγt, retinoid-related orphan receptor γt; RORα, retinoid-related orphan receptor α; T-bet, T-box transcription factor; TGF-β, transforming growth factor-β; TNF, tumour necrosis factor; Treg, T regulator.
Mentions: CD4+ T helper (Th) cells play a critical role in adaptive immune response. After infection or vaccination, naive CD4+ T cells differentiate into diverse effector subsets of Th cells dependent on distinct cytokines and transcription factors [1–5] (Figure 1). These Th cell subsets possess respective effector function, for instance, the antiviral role of Th1 cells and the role in elimination of extracellular parasites of Th2 [2, 3] (Figure 1). Recently, follicular helper CD4+ T (TFH) cells, a specialized subset of CD4+ Th cells, have been identified as providing help for B cells in germinal center (GC) [6, 7]. GC is an important structure in B cell follicles of secondary lymphoid tissues, where B cells can differentiate into plasma cells and memory cells. TFH cells are distinguished from other Th cell subsets by anatomical location (germinal center), specialized expression of transcription factor B cell lymphoma 6 (Bcl-6), chemokine receptor CXC-chemokine receptor 5 (CXCR5), programmed death-1 (PD-1), CD40 ligand (CD40L), inducible costimulator (ICOS), SAP (signaling lymphocytic activation molecule associated protein), and secretion of interleukin 21 (IL-21) and interleukin 4 (IL-4) [8–10]. These TFH-associated molecules are vital for activation, differentiation, and survival of TFH cells and B cells [11]. In a word, TFH cells are pivotal to GC formation, providing help for affinity maturation, class switch recombination, and ultimate differentiation of B cells within GC [12]. The present review outlines the features of TFH cells and TFH-associated molecules in neuroautoimmune diseases, especially in multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG) as well as their animal models, experimental autoimmune encephalomyelitis (EAE), and experimental autoimmune myasthenia gravis (EAMG).

Bottom Line: TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21.It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells.This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The First Hospital of Jilin University, Jilin University, Changchun 130021, China.

ABSTRACT
Follicular helper CD4(+) T (TFH) cells play a fundamental role in humoral immunity deriving from their ability to provide help for germinal center (GC) formation, B cell differentiation into plasma cells and memory cells, and antibody production in secondary lymphoid tissues. TFH cells can be identified by a combination of markers, including the chemokine receptor CXCR5, costimulatory molecules ICOS and PD-1, transcription repressor Bcl-6, and cytokine IL-21. It is difficult and impossible to get access to secondary lymphoid tissues in humans, so studies are usually performed with human peripheral blood samples as circulating counterparts of tissue TFH cells. A balance of TFH cell generation and function is critical for protective antibody response, whereas overactivation of TFH cells or overexpression of TFH-associated molecules may result in autoimmune diseases. Emerging data have shown that TFH cells and TFH-associated molecules may be involved in the pathogenesis of neuroautoimmune diseases including multiple sclerosis (MS), neuromyelitis optica (NMO)/neuromyelitis optica spectrum disorders (NMOSD), and myasthenia gravis (MG). This review summarizes the features of TFH cells, including their development, function, and roles as well as TFH-associated molecules in neuroautoimmune diseases and their animal models.

No MeSH data available.


Related in: MedlinePlus