Spatial and functional heterogeneity of follicular helper T cells in autoimmunity

Seth, Abhinav; Craft, Joe

doi:10.1016/j.coi.2019.06.005

Cited by 39 publications

(44 citation statements)

References 88 publications

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“…The Tfh1 differentiation pathway can be initiated by type 1 responses in which STAT1/4-activating cytokines expand, such as viral infection, vaccination, or some autoimmune diseases ( 9 , 10 , 12 , 13 ). Tfh1-source subsets produce IFN-γ and IL-21 and lead to isotype switching of GC B cells to induce murine IgG 2 or human IgG 1 ( 14 ). Type 2 infections, allergic diseases or autoimmune diseases such as IgG 4 -related disease can initiate Tfh2 differentiation ( 8 , 15 , 16 ).…”

Section: Functional Diversity Of Tfh Cellsmentioning

confidence: 99%

“…Type 2 infections, allergic diseases or autoimmune diseases such as IgG 4 -related disease can initiate Tfh2 differentiation ( 8 , 15 , 16 ). Tfh2-source subsets produce IL-4 and IL-21 to support induction of either murine IgG 1 or human IgG 4 and IgE by GC B cells ( 14 ). Tfh17-source subsets induce IgA production ( 14 ).…”

Section: Functional Diversity Of Tfh Cellsmentioning

confidence: 99%

“…Tfh2-source subsets produce IL-4 and IL-21 to support induction of either murine IgG 1 or human IgG 4 and IgE by GC B cells ( 14 ). Tfh17-source subsets induce IgA production ( 14 ). An increase in circulating Tfh17 cells can be found in patients with immunoglobulin A vasculitis, as well as a variety of immune diseases which are often accompanied by an increase in the Tfh2 subset ( 8 , 10 , 17 ).…”

Section: Functional Diversity Of Tfh Cellsmentioning

confidence: 99%

“…IL-6/IL-21-STAT3 signaling is generally considered as the most desirable factors for Tfh formation, although there is much controversy ( 14 ). At the present, most conclusions supporting this theory have been derived from in vivo experiments.…”

Section: The Roles Of Stat Factors In Early Tfh Differentiationmentioning

confidence: 99%

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Multi-Source Pathways of T Follicular Helper Cell Differentiation

Nakayamada

2021

Front. Immunol.

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T follicular helper (Tfh) cells participate in humoral immune by promoting inflammation and aiding B cells survival, proliferation, maturation, and generation autoantibodies. The plasticity of Tfh cells enables the immune system to adjust the direction of differentiation according to the degree of the immune response, regulate the germinal center (GC) response and maintain homeostasis. Tfh differentiation involves several signaling factors, including multiple cytokines, receptors, transcription factors and genes. The signal transducer and activator of transcription (STAT) family signaling pathways are crucial for Tfh formation. However, because of the multi-factorial and multi-stage features of Tfh differentiation, every STAT member plays a role in Tfh differentiation, but is not completely depended on. With the gradual recognition of different Tfh subsets (Tfh1, Tfh2, Tfh17), the process of Tfh differentiation can no longer be explained by straight-line derivation models. In this review, we summarize the roles of different STATs in mediating Tfh subsets, analyze the contributions of mutual restraint and cooperation among cytokine-STAT signals to terminal Tfh differentiation, and clarify the multi-source pathways of Tfh differentiation with a three-dimensional illustration.

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Section: Functional Diversity Of Tfh Cellsmentioning

confidence: 99%

Section: Functional Diversity Of Tfh Cellsmentioning

confidence: 99%

Section: Functional Diversity Of Tfh Cellsmentioning

confidence: 99%

Section: The Roles Of Stat Factors In Early Tfh Differentiationmentioning

confidence: 99%

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Multi-Source Pathways of T Follicular Helper Cell Differentiation

Nakayamada

2021

Front. Immunol.

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“…Excelentes informações e discussões sobre aspectos específicos podem ser encontradas em revisões recentes. ( 6 , 14 , 26 - 29 , 32 )…”

Section: Introductionunclassified

Human follicular helper T lymphocytes critical players in antibody responses

Alonso¹,

Fomin²,

Rizzo³

2021

Einstein (São Paulo)

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Follicular helper T lymphocytes are a subpopulation of CD4 + T lymphocytes initially identified in germinal centers of follicles found in secondary lymphoid organs. The primary function of follicular helper T lymphocytes is to help B lymphocytes’ antibody production. Changing of antibody class and affinity, B cell differentiation and memory generation depend on cooperation between follicular helper T lymphocytes and B cells. In blood, follicular helper T lymphocytes are called circulating follicular helper T lymphocytes. They are considered to have specificities similar to those developed in the secondary lymphoid organs. The phenotype of human follicular helper T lymphocytes is given by simultaneous expression of the markers CXCR5, Bcl-6, CD40L, PD-1, and ICOS. In germinal centers, follicular helper T lymphocytes synthesize interleukin 21 as predominant cytokine. In blood, subpopulations of circulating follicular helper T lymphocytes can be recognized, with different expressions of the classical follicular helper T lymphocytes markers and, in addition, can express other markers such as CXCR3 and CCR6. Presently, there is great interest in follicular helper T lymphocytes and circulating follicular helper T lymphocytes in vaccination studies as indicators of immunization efficacy. In addition, follicular helper T lymphocytes are investigated as possible markers of activity in many diseases and potential therapeutic intervention. This short review describes aspects of immunobiology and quantification of follicular helper T lymphocytes and circulating follicular helper T lymphocytes, and presents a few examples of related findings in systemic lupus erythematosus, rheumatoid arthritis, HIV infection and vaccination.

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