IL-10 regulates <i>Aicda</i> expression through miR-155

Fairfax, Kirsten; Gantier, Michael P.; Mackay, Fabienne; Williams, Bryan R.G.; McCoy, Claire E.

doi:10.1189/jlb.2a0314-178r

Cited by 24 publications

(16 citation statements)

References 45 publications

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“…This is consistent with our finding that NE inhibitors stimulate IL-10 expression, but also BAFF and APRIL in cultures of splenocytes. IL-10 was reported to regulate expression of AID for induction of Ig CSR [19] and it is wellestablished that IL-10 facilitates Ig class switching for production of IgA [20]. Thus, our data suggest that NE inhibitors stimulate antibody production through stimulation of AID and inhibition of the activation/degradation of cytokines and cytokine receptors by elastase.…”

Section: The Neutrophil Elastase Inhibitors Stimulate Cytokine Signalsupporting

confidence: 57%

Inhibitors of elastase stimulate murine B lymphocyte differentiation into IgG‐ and IgA‐producing cells

et al. 2018

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It is well established that dendritic cells and macrophages play a role in antigen presentation to B and T cells and in shaping B and T cell responses via cytokines they produce. We have previously reported that depletion of neutrophils improves the production of mucosal IgA after sublingual immunization with Bacillus anthracis edema toxin as adjuvant. These past studies also demonstrated that an inverse correlation exists between the number of neutrophils and production of IgA by B cells. Using specific inhibitors of elastase, we addressed whether the elastase activity of neutrophil could be the factor that interferes with production of IgA and possibly other immunoglobulin isotypes. We found that murine splenocytes and mesenteric lymph node cells cultured for 5 days in the presence of neutrophil elastase inhibitors secreted higher levels of IgG and IgA than cells cultured in the absence of inhibitors. The effect of the inhibitors was dose-dependent and was consistent with increased frequency of CD138 cells expressing IgG or IgA. Finally, neutrophil elastase inhibitors increased transcription of mRNA for AID, IL-10, BAFF and APRIL, factors involved in B cell differentiation. These findings identify inhibitors of elastase as potential adjuvants for increasing production of antibodies.

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Section: The Neutrophil Elastase Inhibitors Stimulate Cytokine Signalsupporting

confidence: 57%

Inhibitors of elastase stimulate murine B lymphocyte differentiation into IgG‐ and IgA‐producing cells

et al. 2018

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“…It is unknown which miR-155 targets and pathways are most relevant to our observations, but it is likely that this miR has a cumulative effect on immunity and infection. Recent published findings have shown that miR-155 regulation of AID is important for IL-10-mediated regulation of B cell activation [ 53 ]. Also, SHIP1 was shown to be repressed by miR-155 in BMDMs [ 40 ], which is reversed with the addition of IL-10 [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis

et al. 2015

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MicroRNA-155 has been shown to play a role in immune activation and inflammation, and is suppressed by IL-10, an important anti-inflammatory cytokine. The established involvement of IL-10 in the murine model of Borrelia burgdorferi-induced Lyme arthritis and carditis allowed us to assess the interplay between IL-10 and miR-155 in vivo. As reported previously, Mir155 was highly upregulated in joints from infected severely arthritic B6 Il10-/- mice, but not in mildly arthritic B6 mice. In infected hearts, Mir155 was upregulated in both strains, suggesting a role of miR-155 in Lyme carditis. Using B. burgdorferi-infected B6, Mir155-/-, Il10-/-, and Mir155-/- Il10-/- double-knockout (DKO) mice, we found that anti-inflammatory IL-10 and pro-inflammatory miR-155 have opposite and somewhat compensatory effects on myeloid cell activity, cytokine production, and antibody response. Both IL-10 and miR-155 were required for suppression of Lyme carditis. Infected Mir155-/- mice developed moderate/severe carditis, had higher B. burgdorferi numbers, and had reduced Th1 cytokine expression in hearts. In contrast, while Il10-/- and DKO mice also developed severe carditis, hearts had reduced bacterial numbers and elevated Th1 and innate cytokine expression. Surprisingly, miR-155 had little effect on Lyme arthritis. These results show that antagonistic interplay between IL-10 and miR-155 is required to balance host defense and immune activation in vivo, and this balance is particularly important for suppression of Lyme carditis. These results also highlight tissue-specific differences in Lyme arthritis and carditis pathogenesis, and reveal the importance of IL-10-mediated regulation of miR-155 in maintaining healthy immunity.

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“…It is well documented that miRNAs are also important in the regulation of the immune system. miRNA regulate the production of multiple proinflammatory molecules, such as cytokines at the post-transcriptional level (Fairfax et al, 2015, Quinn and O'Neill, 2014, Hou et al, 2009. miRNAs act to fine-tune the immune system so that the inflammatory response is tightly controlled.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterial Infection

Hofman¹

2016

Infectious Disease and Parasites

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IL-10 regulates Aicda expression through miR-155

Cited by 24 publications

References 45 publications

Inhibitors of elastase stimulate murine B lymphocyte differentiation into IgG‐ and IgA‐producing cells

Inhibitors of elastase stimulate murine B lymphocyte differentiation into IgG‐ and IgA‐producing cells

Antagonistic Interplay between MicroRNA-155 and IL-10 during Lyme Carditis and Arthritis

Mycobacterial Infection

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