Loss of miR‐182 affects B‐cell extrafollicular antibody response

Li, Yanfeng; Ou, Xijun; Xu, Shengli; Jin, Zi‐Bing; Iwai, Naoharu; Lam, Kong-Peng

doi:10.1111/imm.12592

Cited by 19 publications

(33 citation statements)

References 39 publications

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“…Overall, our results do not support the published role for miR-182 in plasmablast differentiation (28), especially the aforementioned results in Mir182 2/2 mice immunized with NP-Ficoll (Fig. 10).…”

Section: Humoral Responses To Both Ti-1 and Ti-2 Ags Do Not Depend Oncontrasting

confidence: 99%

“…Given that miR-182 is so strongly induced upon B cell activation, yet its absence is of debatable consequence (24, 28), we sought to carefully investigate the expression of the entire 183c family. As expected (24,28), vigorous mature miR-182 induction was observed by qPCR in mature B cells stimulated ex vivo ( Fig. 1A).…”

Section: Resultssupporting

confidence: 82%

“…Interestingly, a defective extrafollicular response in Mir182 2/2 mice immunized with NP-CGG and, separately, NP-Ficoll was recently demonstrated using ELISA and ELISpot. The significant reduction observed in the titer of NP-specific IgG1 serum Ab and frequency of NP-specific IgG1-secreting plasmablasts at early time points postimmunization led Li et al (28) to conclude that miR-182 plays a prominent role in promoting extrafollicular plasmablast differentiation. The role of 183c miRNAs in plasmablasts evidently requires further elucidation to resolve these inconsistencies.…”

Section: C Gt/gt Mice Manifest a Trend For Reduced Induction Of Sementioning

confidence: 99%

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The B Cell Activation-Induced miR-183 Cluster Plays a Minimal Role in Canonical Primary Humoral Responses

Pucella

Cols

Yen

et al. 2019

The Journal of Immunology

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Although primary humoral responses are vital to durable immunity, fine-tuning is critical to preventing catastrophes such as autoimmunity, chronic inflammation, and lymphomagenesis. MicroRNA (miRNA)-mediated regulation is particularly well suited for fine-tuning roles in physiology. Expression of clustered paralogous miR-182, miR-96, and miR-183 (collectively, 183c) is robustly induced upon B cell activation, entry into the germinal center, and plasmablast differentiation. 183c GT/GT mice lacking 183c miRNA expression exhibit largely normal primary humoral responses, encompassing class switch recombination, affinity maturation, and germinal center reaction, as well as plasmablast differentiation. Our rigorous analysis included ex vivo class switch recombination and plasmablast differentiation models as well as in vivo immunization with thymus-dependent and thymusindependent Ags. Our work sways the debate concerning the role of miR-182 in plasmablast differentiation, strongly suggesting that 183c miRNAs are dispensable. In the process, we present a valuable framework for systematic evaluation of primary humoral responses. Finally, our work bolsters the notion of robustness in miRNA:target interaction networks and advocates a paradigm shift in miRNA studies.

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Section: Humoral Responses To Both Ti-1 and Ti-2 Ags Do Not Depend Oncontrasting

confidence: 99%

Section: Resultssupporting

confidence: 82%

Section: C Gt/gt Mice Manifest a Trend For Reduced Induction Of Sementioning

confidence: 99%

See 1 more Smart Citation

The B Cell Activation-Induced miR-183 Cluster Plays a Minimal Role in Canonical Primary Humoral Responses

Pucella

Cols

Yen

et al. 2019

The Journal of Immunology

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“…Although a recent study suggested that the immune response to experimental Listeria monocytogenes infection is intact in miR-182 −/− mice 36 our results, using miR-182 −/− on the same C57BL/6 background, do suggest some alterations on the early immune response after cardiac allograft transplantation. Further, the recent studies of Li et al demonstrate that miR-182 deficiency (using knock-out mice) does impair early T cell-dependent immune responses 37 . Taken together, these studies suggest that miR-182 does have a role in T cell function, early after stimulation, but suggest after chronic stimulation/exposure the malleability of the miR networks may compensate for the loss of specific microRNAs.…”

Section: Discussionmentioning

confidence: 99%

Absence of miR-182 Augments Cardiac Allograft Survival

Liang

Kaul

et al. 2017

Transplantation

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Background MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate the posttranscriptional expression of target genes and are important regulators in immune responses. Previous studies demonstrated that the miRNA, miR-182 was significantly increased during allograft rejection. Further, the transcription factor Forkhead box (FOX) protein 1, (FOXO1) was shown to be a target of miR-182. The aim of this study is to further examine the role of miR-182 in alloimmune responses. Methods Transplantation of BALB/c cardiac allografts was performed in C57BL/6, miR-182−/−, B6.129S-H2dlAb1-Ea (MHC II− and CD4+ T cell-deficient) and B6.129S2-Tap1tm1Arp (MHC I− and CD8+ T cell-deficient) mice, with or without CTLA-4Ig administration. T cell phenotype, FOXO1 protein levels and graft infiltrating lymphocytes were determined in C57BL/6 or miR-182−/− mice by flow cytometric analysis, western blot and immunohistochemistry, respectively. Results We now show that T cells, mainly CD4+ are the main cellular source of miR-182 during allograft rejection. In the absence of miR-182, CTLA-4Ig treatment significantly increased allograft survival (31.5 days C57BL/6 vs. 60 days miR-182−/− , P<0.01). Further, CTLA4-Ig treatment inhibits miR-182 expression, increases FOXO1 levels, and reduces the percentage of CD4+CD44hi T cells after transplantation. Fewer T cells infiltrate the cardiac allografts and memory T cells are significantly decreased in allograft recipients deficient in miR-182 with CTLA4-Ig Treatment P<0.01). Conclusions Our findings suggest miR-182 contributes to the T cell responses to alloantigen especially under costimulation blockade. Therapeutics that target specific miRNAs may prove beneficial in transplantation.

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“…does not regulate Tfh cell differentiation and function. 126 Several studies showed that miR-181a regulates the TCR signaling threshold of T-helper cells. [127][128][129][130] miR-181a is highly expressed in thymocytes, where it facilitates positive selection.…”

Section: P Otentialrole Sforother Mirna Sinthereg Ul Ati Onoftfhcelmentioning

confidence: 99%

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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Loss of miR‐182 affects B‐cell extrafollicular antibody response

Cited by 19 publications

References 39 publications

The B Cell Activation-Induced miR-183 Cluster Plays a Minimal Role in Canonical Primary Humoral Responses

The B Cell Activation-Induced miR-183 Cluster Plays a Minimal Role in Canonical Primary Humoral Responses

Absence of miR-182 Augments Cardiac Allograft Survival

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

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