Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b

Cho, Sunglim; Lee, Hyang-Mi; Yu, I-Shing; Choi, Youn Soo; Huang, Hsi‐Yuan; Hashemifar, Somaye; Lin, Ling-Li; Chen, Mei‐Chi; Afanasiev, Nikita D; Khan, Aly A.; Lin, Shu‐Wha; Rudensky, Alexander Y.; Crotty, Shane; Lu, Li-Fan

doi:10.1038/s41467-018-05196-3

Cited by 61 publications

(76 citation statements)

References 58 publications

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“…119 In contrast to the aforementioned studies that were based on miR-146a −/− mice or competitive bone marrow chimeras thereof, the absence of miR-146a specifically in T cells did not alter the frequencies of Tfh and GC B cells in steady state or after immunization. 119 However, a simultaneous deletion of both miR-146a and its paralog miR-146b in T cells, but not deletion of miR-146b alone, resulted in increased levels of Tfh and GC B cells and spontaneous autoimmunity already at steady state and also led to elevated GC reactions after immunization. 119 Likewise, upregulation of the miR-146a target Icos was only observed in mice lacking both miR-146a and miR-146b in T cells, but not in the single knockout animals, suggesting that miR-146a and miR-146b cooperatively regulate Tfh cell differentiation and function.…”

Section: Themir-146family:anegativeregulatorof Tfhcellidentitymentioning

confidence: 85%

“…119 In addition, young mice with B cell-specific deficiency in miR-146a displayed elevated humoral immune responses after immunization. 119 In addition, young mice with B cell-specific deficiency in miR-146a displayed elevated humoral immune responses after immunization.…”

Section: Frequencies Of Gc B Cells and Tfh Cells Increased Gc Numbersmentioning

confidence: 99%

“…119 However, a simultaneous deletion of both miR-146a and its paralog miR-146b in T cells, but not deletion of miR-146b alone, resulted in increased levels of Tfh and GC B cells and spontaneous autoimmunity already at steady state and also led to elevated GC reactions after immunization. 119 However, a simultaneous deletion of both miR-146a and its paralog miR-146b in T cells, but not deletion of miR-146b alone, resulted in increased levels of Tfh and GC B cells and spontaneous autoimmunity already at steady state and also led to elevated GC reactions after immunization.…”

Section: Frequencies Of Gc B Cells and Tfh Cells Increased Gc Numbersmentioning

confidence: 99%

“…118 A recent study showed that B cell-specific deletion of miR-146a is sufficient for the development of spontaneous autoimmunity in aged mice, as these animals displayed higher frequencies of GC B cells and Tfh cells, increased GC numbers and size, and elevated amounts of anti-double-stranded DNA autoantibodies at 6 months of age. 119 In addition, young mice with B cell-specific deficiency in miR-146a displayed elevated humoral immune responses after immunization. 119 In contrast to the aforementioned studies that were based on miR-146a −/− mice or competitive bone marrow chimeras thereof, the absence of miR-146a specifically in T cells did not alter the frequencies of Tfh and GC B cells in steady state or after immunization.…”

Section: Themir-146family:anegativeregulatorof Tfhcellidentitymentioning

confidence: 99%

“…119 In addition, young mice with B cell-specific deficiency in miR-146a displayed elevated humoral immune responses after immunization. 119 In contrast to the aforementioned studies that were based on miR-146a −/− mice or competitive bone marrow chimeras thereof, the absence of miR-146a specifically in T cells did not alter the frequencies of Tfh and GC B cells in steady state or after immunization. 119 However, a simultaneous deletion of both miR-146a and its paralog miR-146b in T cells, but not deletion of miR-146b alone, resulted in increased levels of Tfh and GC B cells and spontaneous autoimmunity already at steady state and also led to elevated GC reactions after immunization.…”

Section: Themir-146family:anegativeregulatorof Tfhcellidentitymentioning

confidence: 99%

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MicroRNA‐mediated regulation of T follicular helper and T follicular regulatory cell identity

Maul

Alterauge

Baumjohann

2019

Immunological Reviews

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Summary T follicular helper (Tfh) cells are critical mediators of germinal center (GC) formation and essential for potent humoral immunity. In contrast, T follicular regulatory (Tfr) cells, which share characteristics of both stimulatory Tfh cells and suppressive regulatory T (Treg) cells, restrain excessive GC responses. Tfh cell differentiation is a multistep process that involves continuous interaction with antigen‐presenting cells, co‐stimulatory signals, an appropriate cytokine milieu, and directed migration toward distinct microanatomical structures. These processes are under the control of several intrinsic and extrinsic regulatory layers that further undergo fine‐tuning by post‐transcriptional mechanisms. MicroRNAs (miRNAs) are small, non‐coding RNAs that have been recognized as important post‐transcriptional regulators. miRNAs are particularly critical for Tfh cell generation, as the differentiation of these cells is completely blocked in the absence of mature miRNAs in vivo. Here, we discuss how miRNAs regulate various aspects of Tfh and Tfr cell differentiation and function and how miRNAs thus shape the identity of these cells.

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Section: Themir-146family:anegativeregulatorof Tfhcellidentitymentioning

confidence: 85%

Section: Frequencies Of Gc B Cells and Tfh Cells Increased Gc Numbersmentioning

confidence: 99%

Section: Frequencies Of Gc B Cells and Tfh Cells Increased Gc Numbersmentioning

confidence: 99%

Section: Themir-146family:anegativeregulatorof Tfhcellidentitymentioning

confidence: 99%

Section: Themir-146family:anegativeregulatorof Tfhcellidentitymentioning

confidence: 99%

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MicroRNA‐mediated regulation of T follicular helper and T follicular regulatory cell identity

Maul

Alterauge

Baumjohann

2019

Immunological Reviews

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March of Mycobacterium: miRNAs intercept host cell CD40 signalling

Chauhan

Dandapat

Sarkar³

et al. 2020

Clin & Trans Imm

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The disease tuberculosis is fatal if untreated. It is caused by the acid-fast bacilli Mycobacterium tuberculosis. Mycobacterium resides and replicates within the alveolar macrophages, causing inflammation and granuloma, wherein macrophage-T cell interactions enhance the inflammation-causing pulmonary caseous lesions. The first interactions between Mycobacterium and the receptors on macrophages decide the fate of Mycobacterium because of phagolysosomal impairments and the expression of several miRNAs, which may regulate CD40 expression on macrophages. While the altered phagolysosomal functions impede antigen presentation to the T cell-expressed antigen receptor, the interactions between the macrophage-expressed CD40 and the T cell-expressed CD40-ligand (CD40L or CD154) provide signals to T cells and Mycobacterium-infected macrophages. These two functions significantly influence the resolution or persistence of Mycobacterium infection. CD40 controls T-cell polarisation and host-protective immunity by eliciting interleukin-12p40, nitric oxide, reactive oxygen species and IFN-c production. Indeed, CD40deficient mice succumb to low-dose aerosol infection with Mycobacterium because of deficient interleukin (IL)-12 production leading to impaired IFN-c-secreting T-cell response. In contrast, despite generating fewer granulomas, the CD40L-deficient mice developed anti-mycobacterial T-cell responses to the levels observed in the wild-type mice. These host-protective responses are significantly subdued by the Mycobacterium-infected macrophage produced TGF-b and IL-10, which promote promycobacterial T-cell responses. The CD40-CD40L-induced counteractive immune responses against Mycobacterium thus present a conundrum that we explain here with a reconciliatory hypothesis. Experimental validation of the hypothesis will provide a rationale for designing anti-tubercular immunotherapy.

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Regulation of follicular T helper cell differentiation in antitumor immunity

Hou

Cao

Lin

et al. 2022

Intl Journal of Cancer

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Follicular T helper (Tfh) cells are a subset of CD4+ T cells that play an important role in the formation of germinal centers and the maturation and differentiation of affinity‐matured B cells. Recent studies have demonstrated important functions of Tfh cells in tertiary lymphoid structures of tumors, revealing great potential of Tfh cells in tumor immunity. However, Tfh development is incompletely understood. The differentiation of Tfh cells is a complex, multistage process regulated at the DNA, RNA and protein levels. This review just summarizes current research on the molecular mechanisms of Tfh cell differentiation to better understand the role of Tfh cells in antitumor immunity.

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Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b

Cited by 61 publications

References 58 publications

MicroRNA‐mediated regulation of T follicular helper and T follicular regulatory cell identity

MicroRNA‐mediated regulation of T follicular helper and T follicular regulatory cell identity

March of Mycobacterium: miRNAs intercept host cell CD40 signalling

Regulation of follicular T helper cell differentiation in antitumor immunity

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