RESUMO
Anti-aging immunity induced by vaccines was recently reported to enable the elimination of senescent cells. However, the initial immune response to vaccination declines with age, and there is evidence that elderly dendritic cells (DCs) have a reduced capacity to stimulate T cells. Identification of alternative anti-aging vaccine is therefore warranted. Here, we developed a DC vaccine that delivers a cationic protein (CP) fused with the seno-antigen peptides Gpnmb (Gpnmb-CP) into DCs. The Gpnmb-CP-pulsed DC vaccine (Gpnmb-CP-DC) efficiently presented antigens and activated CD8+ T cells, leading to enhanced immune cytotoxicity and memory responses in CD8+ T cells. Thus, the targeted anti-aging immunity triggered by Gpnmb-CP-DC has the ability to selectively eliminate senescent adipocytes and effectively improve age-related metabolic abnormalities in both high-fat diet (HFD)-induced young and aged mice models, as well as in natural aging mouse model. In contrast, the Gpnmb-CP protein vaccine exhibits minimal efficacy in aged mice model. Furthermore, we observed a decreased phagocytic capacity for antigens in aging DCs, accompanied by an upregulation of the immune checkpoint PDL1 expression and a noticeable decline in activated CD8+ T cell. Hence, Gpnmb-CP-DC emerges as a promising vaccine candidate, demonstrating the capacity to induce potent anti-aging immunity, mitigating adipose tissue senescence and metabolic abnormalities, while resilient to the senescent environment of the organism.
RESUMO
BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease whose etiology is not yet fully understood, and their course is characterized by periods of exacerbation and remission. In quite a few cases, actual disease remission may also accompany with inflammatory bowel disease (IBS)-like symptoms such as abdominal pain, bloating, flatulence, and diarrhea, may greatly impact quality of life. An army of strong evidence to support the FODMAPs diet (LFD) compounds as an effective dietary approach to IBS treatment. However, there is no significant evidence showing the effectiveness of LFD in treating quiescent IBD and its side effects; this lack of evidence is also an important factor hindering its promotion in the treatment of IBD and its complications. Therefore, this systematic review and meta-analysis will evaluate the efficacy and safety of LFD in the treatment of quiescent IBD patients with IBS-like symptoms. METHOD: We searched the following databases from their establishment until December 2021: PubMed, Web of Science, Embase, Cochrane Library, CNKI, VIP, and Wanfang databases. No restrictions regarding publication date or language were applied. Keywords such as "Crohn's disease," "ulcerative colitis," "inflammatory bowel disease," and "FODMAPs" have been combined for search. Ongoing and unpublished research in the Clinical Trials Registry Research will also be included. At the same time, we will manually search all reference lists from relevant systematic reviews for other eligible studies. The selected studies were randomized controlled clinical trials. We will meta-analyze the selected literature by Review Manager software (REVMAN v5.4 Cochrane Collaboration). Two researchers will independently review the research selection, data extraction, and research quality assessments. Finally, we will observe the outcome measures. RESULTS: This study will provide evidence-based data for TFD treatment of IBD and provide new treatment options for future clinical applications. ETHICS AND DISSEMINATION: The protocol of the systematic review does not require ethical approval because it does not involve humans. This article will be published in peer-reviewed journals and presented at relevant conferences. REGISTRATION NUMBER: INPLASY202220060.