IL-13 Production by Regulatory T Cells Protects against Experimental Autoimmune Encephalomyelitis Independently of Autoantigen

Ochoa‐Repáraz, Javier; Rynda, Agnieszka; Ascon, Miguel; Yang, Xinghong; Kochetkova, Irina; Riccardi, Carol; Callis, Gayle; Trunkle, Theresa; Pascual, David W.

doi:10.4049/jimmunol.181.2.954

Cited by 65 publications

(84 citation statements)

References 55 publications

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“…It has been reported that IL-13 is protective against EAE (13,32,33). IL-13 levels were significantly enhanced in the brains of mice protected against EAE after oral treatment with antibiotics when compared with PBS-and i.p.…”

Section: Cd25mentioning

confidence: 87%

“…Luminex was employed to quantify triplicate sets of samples to measure cytokines (IFN-␥, TNF-␣, MIP-1␣, MIP-1␤, MCP-1, IL-6, IL-17, IL-10, IL-4, and IL-13). Capture ELISA was used to quantify IFN-␥, IL-17, IL-10, and IL-13 from supernatants of cells cultured after FACS sort, as previously described (13). For PCR detection of IL-13 mRNA (R-GGTCCTG TAGATGGCATTGCA; L-GGAGCTGAGCAACATCACACA; Invitrogen) a total of 1.0 g of RNeasy-purified mRNA (Qiagen) was reverse transcribed using MultiScribe RT (Amersham Biosciences).…”

Section: Cytokine Detection By Luminex Elisa and Pcrmentioning

confidence: 99%

“…Recent studies have demonstrated that tolerance induction through oral immunization with foreign Ags can control the development of autoimmune diseases. Oral immunization with a single dose of an attenuated strain of Salmonella typhimurium expressing the CFA/I fimbriae of enterotoxigenic Escherichia coli conferred prophylactic (11) and therapeutic (12,13) protection against EAE in SJL mice. Salmonella-CFA/I elicited FoxP3 ϩ T reg cells (12,13), protective against EAE.…”

mentioning

confidence: 99%

“…Oral immunization with a single dose of an attenuated strain of Salmonella typhimurium expressing the CFA/I fimbriae of enterotoxigenic Escherichia coli conferred prophylactic (11) and therapeutic (12,13) protection against EAE in SJL mice. Salmonella-CFA/I elicited FoxP3 ϩ T reg cells (12,13), protective against EAE. Since these T reg cells induced by Salmonella vaccines were elicited after an oral immunization and protected against an inflammatory neurodegenerative disease, it is tempting to suggest a connection between the immune responses elicited in the gut and the immune consequences that may take place in the periphery and, in the case of EAE, within the CNS.…”

mentioning

confidence: 99%

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Role of Gut Commensal Microflora in the Development of Experimental Autoimmune Encephalomyelitis

Ochoa‐Repáraz¹,

Mielcarz

Ditrio

et al. 2009

The Journal of Immunology

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512

406

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Mucosal tolerance has been considered a potentially important pathway for the treatment of autoimmune disease, including human multiple sclerosis and experimental conditions such as experimental autoimmune encephalomyelitis (EAE). There is limited information on the capacity of commensal gut bacteria to induce and maintain peripheral immune tolerance. Inbred SJL and C57BL/6 mice were treated orally with a broad spectrum of antibiotics to reduce gut microflora. Reduction of gut commensal bacteria impaired the development of EAE. Intraperitoneal antibiotic-treated mice showed no significant decline in the gut microflora and developed EAE similar to untreated mice, suggesting that reduction in disease activity was related to alterations in the gut bacterial population. Protection was associated with a reduction of proinflammatory cytokines and increases in IL-10 and IL-13. Adoptive transfer of low numbers of IL-10-producing CD25+CD4+ T cells (>75% FoxP3+) purified from cervical lymph nodes of commensal bacteria reduced mice and in vivo neutralization of CD25+ cells suggested the role of regulatory T cells maintaining peripheral immune homeostasis. Our data demonstrate that antibiotic modification of gut commensal bacteria can modulate peripheral immune tolerance that can protect against EAE. This approach may offer a new therapeutic paradigm in the treatment of multiple sclerosis and perhaps other autoimmune conditions.

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Section: Cd25mentioning

confidence: 87%

Section: Cytokine Detection By Luminex Elisa and Pcrmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Role of Gut Commensal Microflora in the Development of Experimental Autoimmune Encephalomyelitis

Ochoa‐Repáraz¹,

Mielcarz

Ditrio

et al. 2009

The Journal of Immunology

Self Cite

512

406

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“…Other studies have suggested that IL-13 may be a signal to induce apoptosis of microglia, which removes the inflammatory cells from the brain, and consequently protect the neurons from microgliosis [38, 39]. Furthermore, IL-13 was shown to be neuroprotective in patients with multiple sclerosis as well as in murine experimental autoimmune encephalomyelitis models [40, 41]. The significant increase observed in IL-13 mRNA with palmitate treatment suggested that the IL-13 peptide may act as the mediator of the decrease in TNFα mRNA in mHypoE-46 neurons upon co-culture with the microglia.…”

Section: Discussionmentioning

confidence: 99%

Palmitate Induces an Anti-Inflammatory Response in Immortalized Microglial BV-2 and IMG Cell Lines that Decreases TNFα Levels in mHypoE-46 Hypothalamic Neurons in Co-Culture

et al. 2018

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Background and Objectives: Elevated levels of saturated fatty acids (SFA) induce a state of neuroinflammation in the hypothalamus. It has been suggested that microglia sense palmitate, a prevalent circulating SFA, and act as mediators of this inflammatory process by communicating with neurons, particularly those involved in appetite regulation. In this study, we examined the inflammatory response to palmitate in immortalized microglial cell lines, BV-2 and IMG, and the subsequent effects on inflammatory gene expression in a model of NPY/AgRP neurons, mHypoE-46. Methods: The BV-2 cells were treated with 50 µM palmitate for 4 and 24 h, and the transcriptional regulation of markers for inflammation and cellular stress was assessed using an RT² Profiler PCR Array. Select genes were verified with qRT-PCR. The BV-2 and IMG cells were then co-cultured using 1.0-µm cell culture inserts with an immortalized hypothalamic cell line, mHypoE-46, to investigate potential intercellular communication between microglia and neurons. Results: We found that palmitate increased the mRNA levels of specific inflammatory genes, and a general anti-inflammatory profile was revealed in the microglia cells. The mRNA changes in TNFα at 4 and 24 h in BV-2 cells were abrogated with the toll-like receptor 4 (TLR4) inhibitor, TAK-242, indicating the involvement of TLR4. Co-culture of mHypoE-46 neurons with microglia pre-treated with palmitate resulted in repression of TNFα expression in the hypothalamic neurons. As palmitate significantly increased IL-13 expression in microglia, the effect of this cytokine was tested in mHypoE-46 neurons. The addition of IL-13 to neuronal cultures normalized the palmitate-mediated increase in IL-6 and AgRP expression, suggesting that microglia may protect surrounding neurons, at least in part, through the release of IL-13. Conclusions: These results suggest a potential anti-inflammatory role of microglia towards the palmitate-induced neuroinflammation, and potentially energy homeostasis, in hypothalamic neurons.

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Gut, bugs, and brain: Role of commensal bacteria in the control of central nervous system disease

Ochoa‐Repáraz¹,

Mielcarz

Begum-Haque³

et al. 2011

Annals of Neurology

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148

101

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The mammalian gastrointestinal track harbors a highly heterogeneous population of microbial organisms that are essential for the complete development of the immune system. The gut microbes or "microbiota," coupled with host genetics, determine the development of both local microbial populations and the immune system to create a complex balance recently termed the "microbiome." Alterations of the gut microbiome may lead to dysregulation of immune responses both in the gut and in distal effector immune sites such as the central nervous system (CNS). Recent findings in experimental autoimmune encephalomyelitis, an animal model of human multiple sclerosis, suggest that altering certain bacterial populations present in the gut can lead to a proinflammatory condition that may result in the development of autoimmune diseases, in particular human multiple sclerosis. In contrast, other commensal bacteria and their antigenic products, when presented in the correct context, can protect against inflammation within the CNS.

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IL-13 Production by Regulatory T Cells Protects against Experimental Autoimmune Encephalomyelitis Independently of Autoantigen

Cited by 65 publications

References 55 publications

Role of Gut Commensal Microflora in the Development of Experimental Autoimmune Encephalomyelitis

Role of Gut Commensal Microflora in the Development of Experimental Autoimmune Encephalomyelitis

Palmitate Induces an Anti-Inflammatory Response in Immortalized Microglial BV-2 and IMG Cell Lines that Decreases TNFα Levels in mHypoE-46 Hypothalamic Neurons in Co-Culture

Gut, bugs, and brain: Role of commensal bacteria in the control of central nervous system disease

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