CPT-11 mitigates autoimmune diseases by suppressing effector T cells without affecting long-term anti-tumor immunity.

The incidence of autoimmune diseases has significantly increased over the past 20 years. Excessive host immunoreactions and disordered immunoregulation are at the core of the pathogenesis of autoimmune diseases. The traditional anti-tumor chemotherapy drug CPT-11 is associated with leukopenia. Considering that CPT-11 induces leukopenia, we believe that it is a promising drug for the control of autoimmune diseases. Here, we show that CPT-11 suppresses T cell proliferation and pro-inflammatory cytokine production in healthy C57BL/6 mice and in complete Freund's adjuvant-challenged mice. We found that CPT-11 effectively inhibited T cell proliferation and Th1 and Th17 cell differentiation by inhibiting glycolysis in T cells. We also assessed CPT-11 efficacy in treating autoimmune diseases in models of experimental autoimmune encephalomyelitis and psoriasis. Finally, we proved that treatment of autoimmune diseases with CPT-11 did not suppress long-term immune surveillance for cancer. Taken together, these results show that CPT-11 is a promising immunosuppressive drug for autoimmune disease treatment.

Reactive oxygen species formation and its effect on CD4+ T cell-mediated inflammation.

Reactive oxygen species (ROS) are produced both enzymatically and non-enzymatically in vivo. Physiological concentrations of ROS act as signaling molecules that participate in various physiological and pathophysiological activities and play an important role in basic metabolic functions. Diseases related to metabolic disorders may be affected by changes in redox balance. This review details the common generation pathways of intracellular ROS and discusses the damage to physiological functions when the ROS concentration is too high to reach an oxidative stress state. We also summarize the main features and energy metabolism of CD4+ T-cell activation and differentiation and the effects of ROS produced during the oxidative metabolism of CD4+ T cells. Because the current treatment for autoimmune diseases damages other immune responses and functional cells in the body, inhibiting the activation and differentiation of autoreactive T cells by targeting oxidative metabolism or ROS production without damaging systemic immune function is a promising treatment option. Therefore, exploring the relationship between T-cell energy metabolism and ROS and the T-cell differentiation process provides theoretical support for discovering effective treatments for T cell-mediated autoimmune diseases.

Regulatory T cell therapy suppresses inflammation of oral mucosa.

Oral inflammatory diseases, including oral lichen planus (OLP) and recurrent aphthous ulcer (RAU), seriously affect the patient's quality of life. Due to the lack of ideal disease models, it is difficult to determine whether novel immunotherapy strategies are effective in treating oral inflammatory diseases. Here, we show that the deficiency of Foxp3 or IL-2 caused oral mucosa inflammation in mice, proving that Treg cells are important in maintaining the immune homeostasis in the oral mucosa. Then we determined that adoptive transfer of CD4+CD25-CD45Rbhigh T cells could induce oral inflammation in Rag1 -/- mice, and co-transfer of Treg cells together with CD4+CD25-CD45Rbhigh T cells could suppress the development of oral inflammation in this mouse model. Our study showed that adoptive transfer of CD4+CD25-CD45Rbhigh T cells into Rag1 -/- mice could be a novel disease model of oral inflammation. Our data provides direct evidence that Treg cell therapy is effective in suppressing oral mucosa inflammation in mice. Therefore, Treg cell therapy may be a promising novel strategy to treat oral inflammatory diseases.

Excessive intake of sugar: An accomplice of inflammation.

High sugar intake has long been recognized as a potential environmental risk factor for increased incidence of many non-communicable diseases, including obesity, cardiovascular disease, metabolic syndrome, and type 2 diabetes (T2D). Dietary sugars are mainly hexoses, including glucose, fructose, sucrose and High Fructose Corn Syrup (HFCS). These sugars are primarily absorbed in the gut as fructose and glucose. The consumption of high sugar beverages and processed foods has increased significantly over the past 30 years. Here, we summarize the effects of consuming high levels of dietary hexose on rheumatoid arthritis (RA), multiple sclerosis (MS), psoriasis, inflammatory bowel disease (IBD) and low-grade chronic inflammation. Based on these reported findings, we emphasize that dietary sugars and mixed processed foods may be a key factor leading to the occurrence and aggravation of inflammation. We concluded that by revealing the roles that excessive intake of hexose has on the regulation of human inflammatory diseases are fundamental questions that need to be solved urgently. Moreover, close attention should also be paid to the combination of high glucose-mediated immune imbalance and tumor development, and strive to make substantial contributions to reverse tumor immune escape.

Mannose: A Sweet Option in the Treatment of Cancer and Inflammation.

As a natural sugar, mannose is a type of hexose that is abundant in many different types of fruits. Since mannose is rarely used for glycolysis in mammals, studies on the role of mannose have not attracted much attention. Glycosylation of specific proteins was thought to be the major function of mannose. Surprisingly, during the past few years, mannose was found to be effective in promoting immune tolerance and suppressing inflammatory diseases related to autoimmunity and allergy. Moreover importantly, mannose was also found to be efficient in suppressing tumors by suppressing glycolysis and enhancing chemotherapeutic agents. In this review, we summarize the recent studies of mannose on antitumor properties and anti-inflammatory characteristics. We emphasize that mannose could play a beneficial role in the treatment of a variety of diseases, including cancers and inflammatory diseases, and could be a novel therapeutic strategy that deserves continued evaluation.