Interleukin 10 modulation of pathogenic Th17 cells during fatal alphavirus encephalomyelitis

Kulcsar, Kirsten A.; Baxter, Victoria K.; Greene, Ivorlyne P.; Griffin, Diane E.

doi:10.1073/pnas.1418966111

Cited by 66 publications

(81 citation statements)

References 50 publications

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“…Infective agents are also IL-10 producers that co-opt or manipulate immune response of the host for their benefits, whereas in some cases, the downregulation of mentioned cytokine under effect of diverse Th milieus may lead to supplemental tissue damage up to lethal outcome [38, 43, 68, 69, [90][91][92][93].…”

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

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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.

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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

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“…GM-CSF activates microglial cells and recruits myeloid cells into the CNS, but the mechanism by which this leads to disease has not been identified [47,50,51]. Furthermore, neutralizing antibody to neither GM-CSF nor IL-17 altered the course of disease compared with control antibody in either IL-10 −/− or wild-type mice [39].…”

Section: Role Of Virus Strainmentioning

confidence: 99%

“…Deficiency of IL-10 accelerates the onset of fatal NSV-induced paralytic disease with an early increase in the CNS of CD4 + T cells expressing the transcription factor RORγt and producing the cytokine IL-17 [T helper (Th) 17 cells] [39]. Th17 cells are multifunctional and can have pathogenic or nonpathogenic characteristics.…”

Section: Role Of Virus Strainmentioning

confidence: 99%

Alphavirus Encephalomyelitis: Mechanisms and Approaches to Prevention of Neuronal Damage

Griffin

2016

Neurotherapeutics

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Mosquito-borne viruses are important causes of death and long-term neurologic disability due to encephalomyelitis. Studies of mice infected with the alphavirus Sindbis virus have shown that outcome is dependent on the age and genetic background of the mouse and virulence of the infecting virus. Agedependent susceptibility reflects the acquisition by neurons of resistance to virus replication and virus-induced cell death with maturation. In mature mice, the populations of neurons most susceptible to infection are in the hippocampus and anterior horn of the spinal cord. Hippocampal infection leads to long-term memory deficits in mice that survive, while motor neuron infection can lead to paralysis and death. Neuronal death is immune-mediated, rather than a direct consequence of virus infection, and associated with entry and differentiation of pathogenic T helper 17 cells in the nervous system. To modulate glutamate excitotoxicity, mice were treated with an N-methyl-D-aspartate receptor antagonist, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonists or a glutamine antagonist. The N-methyl-D-aspartate receptor antagonist MK-801 protected hippocampal neurons but not motor neurons, and mice still became paralyzed and died. α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonists GYKI-52466 and talampanel protected both hippocampal and motor neurons and prevented paralysis and death. Glutamine antagonist 6-diazo-5-l-norleucine protected hippocampal neurons and improved memory generation in mice surviving infection with an avirulent virus. Surprisingly, in all cases protection was associated with inhibition of the antiviral immune response, reduced entry of inflammatory cells into the central nervous system, and delayed virus clearance, emphasizing the importance of treatment approaches that include prevention of immunopathologic damage.

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“…469 IL-17, a cytokine produced by Th17 T cells, has been detected in 470 several cohorts of CHIKF patients Chow et al, 471 2011;Teng et al, 2015). Th17 cells have been shown to play patho-472 genic roles in other alphaviral infections (Kulcsar et al, 2014), and 473 in rheumatoid arthritis (RA) patients (Kotake et al, 1999;Chabaud 474 et al, 2000). Given that the disease outcome of RA is quite similar 475 to CHIKV infection (Nakaya et al, 2012), it would be interesting to (Table 1).…”

mentioning

confidence: 99%

Cellular and molecular mechanisms of chikungunya pathogenesis

Lum

2015

Antiviral Research

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Interleukin 10 modulation of pathogenic Th17 cells during fatal alphavirus encephalomyelitis

Cited by 66 publications

References 50 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

Alphavirus Encephalomyelitis: Mechanisms and Approaches to Prevention of Neuronal Damage

Cellular and molecular mechanisms of chikungunya pathogenesis

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