ABSTRACT
Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.
Subject(s)
Animals , Mice , Aging , Autoimmune Diseases , Disease Models, Animal , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Mice, Inbred C57BL , Th17 Cells/metabolism , Uveitis/pathology , VirulenceABSTRACT
Objective To study the effects of apoptosis of the tumor cells in rabbit liver VX2 carcinoma after treatment by radiofrequency ablation(RFA) combined with trans arterial chemoembolization(TACE) and high‐frequency hyperthermia(HFH) . Methods Rabbit liver VX2 carcinoma model was established .Rabbit liver VX2 tumor models were divided into the following group:group A ,RFA+ TACE;group B ,RFA + TACE + HFH ;group C ,RFA + HFH ;group D ,TACE+ HFH .The changes of serum ALT was detected to realize the safety of the treatment .Cell apoptosis were detected by DNA agarose gel electrophoresis and terminal deoxynucleotidyltransferase‐mediated Dutp nick end‐labeling(TUNEL) assay ;SP immunohistochemistry ,Western blot and Real‐time quantitative PCR(RT‐PCR) were used to detect Caspase‐3 protein and mRNA expression levels .Results The changes of serum ALT in group B was significantly higher .Compared with other groups ,the apoptosis index in group B was increased marked‐ly(P<0 .05) .Western blot and RT‐PCR Caspase‐3 protein and mRNA levels in group B were higher than the other groups(P<0 .05) .Conclusion RFA+ TACE+ HFH can effectively kill tumor cells and promote apoptosis of tumor cells ,but ,at the same time ,can damage liver function .
ABSTRACT
Objective:To investigate the role of NF-kB activation in the development of multiple organ dysfunction (MOD) during acute obstructive cholangitis (AOC) in rats.Methods:42 Wistar rats were divided into three groups:the AOC group,the group of bile duct ligation (BDL group),and the sham operation group (SO group).All the animals were killed at 6th h or 48th h after operation.Morphological changes in vital organs were observed under light and electron microscope.NF-?B activation was determined with Electrophoretic Mobility Shift Assay (EMSA).Arterial blood gas analysis was performed.Other parameters included the serum levels of lactate dehydrogenase (LDH),alanine aminotransferase (ALT),blood urea nitrogen (BUN),creatinine (Cr) and the plasma levels of TNF-? and IL-6.Results: The significant changesinhistology and ultrastructure of vitalorgans were observedin AOC group .By contrast ,inBDLgroup ,allthefeaturesoforgandamageweregreatlyreduced .NF -?Bactivationinvarioustissues markedlyin creased in AOC group when comparedwith other two groups.Inaddition ,there sults of bloodgasanalysis were obviously abnormalin AOC group ,and there was asignificant difference between AOC an do the rgroups (P