An immune-modulating diet increases the regulatory T cells and reduces T helper 1 inflammatory response in Leishmaniosis affected dogs treated with standard therapy

Abstract Background CD4+CD25+ regulatory T cells (Tregs) play an essential role in sepsis-induced immunosuppression. How, the effects of interleukin 36 (IL-36) cytokines on CD4+CD25+ Tregs and their underlying mechanism(s) in sepsis remain unknown. Methods Our study was designed to investigate the impacts of IL-36 cytokines on murine CD4+CD25+ Tregs in presence of lipopolysaccharide (LPS) and in a mouse model of sepsis induced by cecal ligation and puncture (CLP). IL-36–activated autophagy was evaluated by autophagy markers, autophagosome formation, and autophagic flux. Results IL-36α, IL-36β, and IL-36γ were expressed in murine CD4+CD25+ Tregs. Stimulation of CD4+CD25+ Tregs with LPS markedly up-regulated the expression of these cytokines, particularly IL-36β. IL-36β strongly suppressed CD4+CD25+ Tregs under LPS stimulation and in septic mice challenged with CLP, resulting in the amplification of T-helper 1 response and the proliferation of effector T cells. Mechanistic studies revealed that IL-36β triggered autophagy of CD4+CD25+ Tregs. These effects were significantly attenuated in the presence of the autophagy inhibitor 3-methyladenine or Beclin1 knockdown. In addition, early IL-36β administration reduced the mortality rate in mice subjected to CLP. Depletion of CD4+CD25+ Tregs before the onset of sepsis obviously abrogated IL-36β–mediated protection against sepsis. Conclusions These findings suggest that IL-36β diminishes the immunosuppressive activity of CD4+CD25+ Tregs by activating the autophagic process, thereby contributing to improvement of the host immune response and prognosis in sepsis.

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Neuroenteric axis modulates the balance of regulatory T cells and T-helper 17 cells in the mesenteric lymph node following trauma/hemorrhagic shock

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00097.2015 ◽

2015 ◽

Vol 309 (3) ◽

pp. G202-G208 ◽

Cited By ~ 19

Author(s):

Koji Morishita ◽

Raul Coimbra ◽

Simone Langness ◽

Brian P. Eliceiri ◽

Todd W. Costantini

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Inflammatory Response ◽

Hemorrhagic Shock ◽

Th17 Cell ◽

Male Rats ◽

T Helper ◽

Mesenteric Lymph Nodes ◽

T Helper 17 ◽

Mesenteric Lymph

CD103+ dendritic cells (DCs) continuously migrate from the intestine to the mesenteric lymph nodes (MLNs) and maintain tolerance by driving the development of regulatory T cells (Treg) in the gut. The relative expression of Treg and T-helper 17 (Th17) cells determines the balance between tolerance and immunity in the gut. We hypothesized that trauma/hemorrhagic shock (T/HS) would decrease the CD103+ DC population in the mesenteric lymph and alter the Treg-to-Th17 ratio in the MLN. We further hypothesized that vagus nerve stimulation (VNS) would promote tolerance to inflammation by increasing the Treg-to-Th17 ratio in the MLN after injury. Male rats were assigned to sham shock (SS), trauma/sham shock (T/SS), or T/HS. T/HS was induced by laparotomy and 60 min of HS (blood pressure 35 mmHg) followed by fluid resuscitation. A separate cohort of animals underwent cervical VNS after the HS phase. MLN samples were collected 24 h after resuscitation. The CD103+ DC population and Treg-to-Th17 cell ratio in the MLN were decreased after T/HS compared with SS and T/SS, suggesting a shift to an inflammatory response. VNS prevented the T/HS-induced decrease in the CD103+ DC population and increased the Treg-to-Th17 ratio compared with T/HS alone. VNS alters the gut inflammatory response to injury by modulating the Treg-Th17 cell balance in the MLN. VNS promotes tolerance to inflammation in the gut, further supporting its ability to modulate the inflammatory set point and alter the response to injury.

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Radon Therapy for Autoimmune Diseases Pemphigus and Diabetes: 2 Case Reports

Dose-Response ◽

10.1177/1559325819850984 ◽

2019 ◽

Vol 17 (2) ◽

pp. 155932581985098 ◽

Cited By ~ 5

Author(s):

Shuji Kojima ◽

Jerry M. Cuttler ◽

Noriko Shimura ◽

Hironobu Koga ◽

Akihisa Murata ◽

...

Keyword(s):

T Cells ◽

Regulatory T Cells ◽

Autoimmune Diseases ◽

Type I Diabetes ◽

Case Reports ◽

Type I ◽

T Helper ◽

T Helper 1 ◽

Normal Ranges ◽

Cell Balance

We report on the application of radon therapy to relieve the suffering of 2 patients with autoimmune diseases, one with pemphigus with an old myocardial infarction and diabetes mellitus and the other with type I diabetes. We include a lengthy discussion of the biological mechanisms that we believe produced the observed benefits. During the 6 to 9 months of the treatments, the marker values decreased to the upper limit of their normal ranges and the symptoms of the diseases were alleviated. Disorders of Th1/Th2 balance are implicated in the onset of many diseases, including autoimmune diseases. Our decision to give radon (222Rn) therapy to these patients was based on the results of 2 similar case reports and our earlier mouse experiments, which indicated that low doses of radiation induce regulatory T cells. Regulatory T cells regulate the T helper 1 cell and the T helper 2 cell balance. There are more than 80 different autoimmune diseases that are treated with anti-inflammatory agents or immune-suppressing drugs because the exact causes of these diseases and the cures are unknown. These and other case reports indicate that proper radon therapy is an effective treatment. We urge physicians to consider radon as a standard therapy for refractory autoimmune diseases.

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