Involvement of Suppressive B-Lymphocytes in the Mechanism of Tolerogenic Dendritic Cell Reversal of Type 1 Diabetes in NOD Mice

Di, Valentina; Phillips, Brett E.; Engman, Carl; Harnaha, Jo; Trucco, Massimo; Giannoukakis, Nick

doi:10.1371/journal.pone.0083575

Cited by 42 publications

(46 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The IL-10 increase is also demonstrated during treatment with anti-inflammatory agents like ellagic acid or meloxicam, while B cell-induced IL-10 secretion by Tregs or DCs is associated with recovery of Kawasaki Disease (KD), nonobese diabetes, MS, autoimmune thyroiditis (AT), etc. [110][111][112][113][114]. With respect to systemic lupus erythematous (SLE), both the percentage of circulating Breg cells and the ability to produce IL-10 were elevated; the percentage of Breg cells increased during SLE flares and decreased following disease remission [115].…”

Section: Principal Immune Conditionsmentioning

confidence: 99%

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Mingomataj

Bakiri

2015

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

The interleukin-10 (IL-10) is generally considered as the most important cytokine with anti-inflammatory properties and one of the key cytokines preventing inflammation-mediated tissue damage. In this respect, IL-10 producing cells play a crucial role in the outcome of infections, allergy, autoimmune reactions, tumor development, and transplant tolerance. Based on recent findings with regard to the mentioned clinical conditions, this review attempts to shed some light on the IL-10 functions, considering this cytokine as inherent inducer of the switching immunity. While acute infections and vaccinations are associated by IL-10 enhanced during few weeks, chronic parasitoses, tumor diseases, allergen-specific immunotherapy, transplants, and use of immune-suppressor drugs show an increased IL-10 level along months or years. With regard to autoimmune pathologies, the IL-10 increase is prevalently observed during early stages, whereas the successive stages are characterized by reaching of immune equilibrium independently to disease's activity. Together, these findings indicate that IL-10 is mainly produced during transient immune conditions and the persistent IL-10-related effect is the indication/prediction (and maybe effectuation) of the switching immunity. Actual knowledge emphasizes that any manipulation of the IL-10 response for treatment purposes should be considered very cautiously due to its potential hazards to the immune system. Probably, the IL-10 as potential switcher of immunity response should be used in association with co-stimulatory immune effectors that are necessary to determine the appropriate deviation during treatment of respective pathologies. Hopefully, further findings would open new avenues to study the biology of this "master switch" cytokine and its therapeutic potential.

show abstract

Section: Principal Immune Conditionsmentioning

confidence: 99%

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Mingomataj

Bakiri

2015

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

show abstract

“…Of note is the observation of increased B cells in ladarixin-treated NOD mice. The role of B cells in the modulation of islet immune cell responses has been recently recognized in models of autoimmune diabetes (46,47) and immunomodulatory effects of Gr-1 + CD11b + cells were reported in NOD mice receiving anti-CD20 treatment (48). In addition, IL-9, IL-6, and IL-12p70 were modified by CXCR1/2 inhibitor treatment in relation to the different disease phases.…”

Section: Diabetesdiabetesjournalsorgmentioning

confidence: 99%

CXCR1/2 Inhibition Blocks and Reverses Type 1 Diabetes in Mice

et al. 2014

View full text Add to dashboard Cite

Chemokines and their receptors have been associated with or implicated in the pathogenesis of type 1 diabetes (T1D), but the identification of a single specific chemokine/receptor pathway that may constitute a suitable target for the development of therapeutic interventions is still lacking. Here, we used multiple low-dose (MLD) streptozotocin (STZ) injections and the NOD mouse model to investigate the potency of CXCR1/2 inhibition to prevent inflammation- and autoimmunity-mediated damage of pancreatic islets. Reparixin and ladarixin, noncompetitive allosteric inhibitors, were used to pharmacologically blockade CXCR1/2. Transient blockade of said receptors was effective in preventing inflammation-mediated damage in MLD-STZ and in preventing and reversing diabetes in NOD mice. Blockade of CXCR1/2 was associated with inhibition of insulitis and modification of leukocytes distribution in blood, spleen, bone marrow, and lymph nodes. Among leukocytes, CXCR2+ myeloid cells were the most decreased subpopulations. Together these results identify CXCR1/2 chemokine receptors as “master regulators” of diabetes pathogenesis. The demonstration that this strategy may be successful in preserving residual β-cells holds the potential to make a significant change in the approach to management of human T1D.

show abstract

“…Conversely, IL-10-deficient DCs exhibited impaired capacity to induce tolerance to myelin P0. Induction of regulatory B cells such as B10 cells by tolerogenic DCs has recently been reported not only in NOD mice, but also in phase 1 clinical trial of tolerogenic autologous DC administration in type 1 diabetes (51, 52). In our current study, increased frequency of Tregs without concomitant increased frequency of B10 cells is sufficient to induce tolerance to myelin P0, as observed in animals tolerized with antigen-pulsed WT DCs.…”

Section: Discussionmentioning

confidence: 99%

“…The tolerogenic effect of IL-10-conditioned DCs has been reported in other models such as type 1 diabetes in NOD mice and rheumatoid arthritis models (58, 59). Aside from IL-10, tolerogenic DCs can also be induced in vitro by rapamycin, dexamethasone, TGF-β1, Vitamin D3, retinoic acid, inducers of cyclic AMP or by antisense oligonucleotide targeting CD40, CD80 and CD86 (52, 60). Recently, B7-2 deficient bone marrow DCs transduced with lentiviral vectors expressing vasoactive intestinal peptide (LV-VIP-BCD11b + DCs) has been shown to delay the onset of disease and attenuate clinical severity in SAP (61).…”

Section: Discussionmentioning

confidence: 99%

Impaired Dendritic Cell Function in a Spontaneous Autoimmune Polyneuropathy

Quan

Kim

Dukala

et al. 2015

The Journal of Immunology

View full text Add to dashboard Cite

Spontaneous autoimmune polyneuropathy (SAP) in B7-2 knockout non-obese diabetic (NOD) mice mimics the progressive form of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and is mediated by myelin P0-reactive Th1 cells. In this study, we focused on the effect of B7-2 deletion on the function of dendritic cells (DCs) within the context of SAP. We found that development of SAP was associated with a preponderance or increase of CD11b+ DCs in peripheral lymph nodes and sciatic nerves. B7-2 deletion led to altered immunophenotypic properties that differ between CD11b+ DCs and CD8α+ DCs. Both DC subsets from B7-2 knockout (KO) NOD mice exhibited impaired capacity to capture fluorophore-labeled myelin P0, but diminished antigen-presenting function was observed only in CD11b+ DCs. Clinical assessment, electrophysiologic studies and splenocyte proliferation studies revealed that absence of B7-2 on DCs was sufficient to cause impaired ability to induce tolerance to P0, which could be overcome by pre-conditioning with interleukin-10 (IL-10). Tolerance induction by antigen-pulsed WT NOD DCs was dependent on IL-10 and was associated with increased CD4+ regulatory T cells (Tregs), whereas tolerance induction by IL-10-conditioned B7-2 deficient DCs was associated with increased percentages of both Tregs and B10 cells in the spleen. We conclude that B7-2 deletion has an impact on the distribution of DC subsets in lymphoid organs, and alters the expression of co-stimulatory molecules, but functional consequences are not uniform across DC subsets. Defective tolerance induction in the absence of B7-2 can be restored by preconditioning of DCs with IL-10.

show abstract

Involvement of Suppressive B-Lymphocytes in the Mechanism of Tolerogenic Dendritic Cell Reversal of Type 1 Diabetes in NOD Mice

Cited by 42 publications

References 99 publications

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

CXCR1/2 Inhibition Blocks and Reverses Type 1 Diabetes in Mice

Impaired Dendritic Cell Function in a Spontaneous Autoimmune Polyneuropathy

Contact Info

Product

Resources

About