Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseases

He, Hao; Nakayamada, Shingo; Tanaka, Yoshiya

doi:10.1186/s41232-021-00164-9

Cited by 22 publications

(17 citation statements)

References 95 publications

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“…4 A to C, and Supplementary Data 12 ) 36 – 38 . These follicular-like regulatory CD4 + T cell subsets have been postulated as critical regulators of adaptive responses in lymphoid organs 39 – 41 , but so far have not been reported in the brain during infections. These populations seemed dynamic over the course of infection, with chronic stages associated with a 1.27- and 1.61-fold increase in the abundance of Cd4 + T cells compared to other subclusters (23.64%, 30.21%, and 38.1% in naïve, 25dpi, and 45dpi, respectively) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection

et al. 2022

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Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei and induces profound reactivity of glial cells and neuroinflammation when the parasites colonise the central nervous system. However, the transcriptional and functional responses of the brain to chronic T. brucei infection remain poorly understood. By integrating single cell and spatial transcriptomics of the mouse brain, we identify that glial responses triggered by infection are readily detected in the proximity to the circumventricular organs, including the lateral and 3rd ventricle. This coincides with the spatial localisation of both slender and stumpy forms of T. brucei. Furthermore, in silico predictions and functional validations led us to identify a previously unknown crosstalk between homeostatic microglia and Cd138+ plasma cells mediated by IL-10 and B cell activating factor (BAFF) signalling. This study provides important insights and resources to improve understanding of the molecular and cellular responses in the brain during infection with African trypanosomes.

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Section: Resultsmentioning

confidence: 99%

Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection

et al. 2022

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“…Moreover, ICOS stimulation induces RORC2 and c-Maf expression in Th17 cells and Bcl-6 expression in TFH cells, leading to increased secretion of IL-17 and IL-21, respectively [ 56 , 61 ]. What is more, ICOS ligation upregulates transcription factors FOXP3 and Bcl-6 and promotes IL-10 and TGF- β production in TFR cells [ 62 ] ( Figure 2 ).…”

Section: Inducible Costimulator (Icos)mentioning

confidence: 99%

Follicular Helper CD4+ T Cells, Follicular Regulatory CD4+ T Cells, and Inducible Costimulator and Their Roles in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Zhang

Chen

et al. 2021

Mediators of Inflammation

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Follicular helper CD4+ T (TFH) cells are a specialized subset of effector T cells that play a central role in orchestrating adaptive immunity. TFH cells mainly promote germinal center (GC) formation, provide help to B cells for immunoglobulin affinity maturation and class-switch recombination of B cells, and facilitate production of long-lived plasma cells and memory B cells. TFH cells express the nuclear transcriptional repressor B cell lymphoma 6 (Bcl-6), the chemokine (C-X-C motif) receptor 5 (CXCR5), the CD28 family members programmed cell death protein-1 (PD-1) and inducible costimulator (ICOS) and are also responsible for the secretion of interleukin-21 (IL-21) and IL-4. Follicular regulatory CD4+ T (TFR) cells, as a regulatory counterpart of TFH cells, participate in the regulation of GC reactions. TFR cells not only express markers of TFH cells but also express markers of regulatory T (Treg) cells containing FOXP3, glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T lymphocyte antigen 4 (CTLA-4), and IL-10, hence owing to the dual characteristic of TFH cells and Treg cells. ICOS, expressed on activated CD4+ effector T cells, participates in T cell activation, differentiation, and effector process. The expression of ICOS is highest on TFH and TFR cells, indicating it as a key regulator of humoral immunity. Multiple sclerosis (MS) is a severe autoimmune disease that affects the central nervous system and results in disability, mediated by autoreactive T cells with evolving evidence of a remarkable contribution from humoral responses. This review summarizes recent advances regarding TFH cells, TFR cells, and ICOS, as well as their functional characteristics in relation to MS.

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“…Notably, these regulatory Cd4 + T cells also express high levels of marker genes typically associated with follicular helper T cells such as Maf and Slamf5 ( Figure 4A to 4C, and S2I Table ) (Bauquet et al, 2009; Cannons et al, 2010; Nurieva and Chung, 2010). These follicular-like regulatory CD4 + T cell subsets have been postulated as critical regulators of adaptive responses in lymphoid organs (Hao et al, 2021a; Miles and Connick, 2018; Vaeth et al, 2019, 2019; Wollenberg et al, 2011), but so far have not been reported in the brain during infections. These populations seemed dynamic over the course of infection, with chronic stages associated with a two-fold increase in the abundance of Cd4 + T cells compared to other subclusters (8.2%, 19.3%, and 20.85% in naïve, 25dpi, and 45dpi, respectively) ( Figure 4B and 4D ), consistent with previous reports (Laperchia et al, 2016; Lyck et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

Integrative single cell and spatial transcriptomic analysis reveal reciprocal microglia-plasma cell crosstalk in the mouse brain during chronicTrypanosoma bruceiinfection

Quintana

Chandrasegaran

Sinton

et al. 2022

Preprint

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Human African trypanosomiasis, or sleeping sickness, is caused by the protozoan parasite Trypanosoma brucei, and induces profound reactivity of glial cells and neuroinflammation when the parasites colonise the central nervous system. However, the transcriptional and functional responses of the brain to chronic T. brucei infection remain poorly understood. By integrating single cell and spatial transcriptomics of the mouse brain, we identified that glial responses triggered by infection are readily detected in the proximity to the circumventricular organs, including the lateral and 3rd ventricle, coinciding with the spatial localisation of both slender and stumpy forms of T. brucei. Furthermore, in silico predictions and functional validations led us to identify a previously unknown crosstalk between homeostatic Cx3cr1+ microglia and Cd138+ plasma cells mediated by IL-10 and B cell activating factor (BAFF) signalling. This study provides important insights and resources to improve understanding of the molecular and cellular responses triggered in the brain upon infection with African trypanosomes.

show abstract

Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseases

Cited by 22 publications

References 95 publications

Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection

Single cell and spatial transcriptomic analyses reveal microglia-plasma cell crosstalk in the brain during Trypanosoma brucei infection

Follicular Helper CD4+ T Cells, Follicular Regulatory CD4+ T Cells, and Inducible Costimulator and Their Roles in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

Integrative single cell and spatial transcriptomic analysis reveal reciprocal microglia-plasma cell crosstalk in the mouse brain during chronicTrypanosoma bruceiinfection

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