Detection and genetic characterization of circulating canine parvovirus from stray dogs in Shanghai, China.

Canine parvovirus (CPV) is the main cause of viral diarrhea in dogs. CPV became a global disease in 1978 and was endemic all over the world. CPV-2 was the first strain to be identified, but with genetic mutations, new genotypes such as CPV-2a/2b/2c/new-2a/new-2b have emerged. In this study, 128 fecal samples of stray dogs suspected of CPV-2 infection were collected from January to March 2021 in Shanghai, China. All samples were screened by PCR and further analyzed by VP2 gene. The positive rate of CPV-2 was 9.4% (12/128), of which 6 CPV-2 isolates were successfully isolated. Phylogenetic tree analysis showed that 4 isolates were CPV-2c genotype and 2 were new-CPV-2b genotype. VP-2 is a key protein that determines the antigenic properties, host range and receptor binding of cpv-2. The results of VP2 amino acid sequence analysis in this study showed that the CPV-2c isolated strain was the same as the previous strains reported in China, including F267Y, Y324I, Q370R and A5G mutations in addition to the typical N426E mutations. Similarly, in addition to the conventional N426D, S297A, F267Y and Y324I mutations, the new CPV-2b isolate also had a new mutation of T440A. This study further confirmed the prevalence of CPV-2c and new-CPV-2b in Shanghai, and also found a new mutation site of new-CPV-2c, which provided a theoretical basis for further enriching the epidemiological data of CPV-2 in Shanghai, as well as the development of vaccines and the prevention and control of the disease.

Quercetin attenuates inflammation in LPS-induced lung epithelial cells via the Nrf2 signaling pathway.

BACKGROUND: Pneumonia is the leading cause of death among children under five, and kill almost two million children each year. Quercetin, a flavonoid polyphenolic compound, exerts many beneficial biological activities, including anti-inflammatory functions. Our study aimed to investigate the possibility of quercetin as a therapeutic agent for pneumonia and its role in the inflammatory response induced by lipopolysaccharide (LPS). METHODS: LPS induced human alveolar epithelial cell A549 as a lung inflammation model in vitro. The effects of quercetin on the production of cytokines and the expression of related-proteins were detected by Enzyme-Linked ImmunoSorbent Assay and Western Blot, respectively. Cell Counting Kit-8 assay was used to detect cell viability. flow cytometry was used to measure cell apoptosis. NO levels were also analyzed through NO kit. RESULTS: Our results found that quercetin attenuated the release of IL-1ß, IL-6, PGE2, and nitrite in LPS-induced A549 cells. In addition, quercetin inhibits cell apoptosis and relieves ROS generation in LPS-induced A549 cells. Quercetin also inhibits LPS-induced NF-κB activation. They have upregulated the expression of nuclear factor erythroid 2 (Nrf2) and HO-1. CONCLUSION: In conclusion, these results suggested that quercetin attenuates LPS-induced inflammation in A549 by activating the Nrf2 signaling pathway.

The Potential of Berberine to Target Telocytes in Rabbit Heart.

A brand-new class of interstitial cells, called telocytes, has been detected in the heart. Telocytes can connect and transmit signals to almost all cardiomyocytes; this is highly interrelated with the occurrence and development of heart diseases. Modern studies have shown that berberine has a therapeutic effect on cardiovascular health. However, berberine's mechanism of action on the cardiovascular system through cardiac telocytes is unclear. Interestingly, 5 µm of berberine remarkably decreased the concentration of intracellular calcium and membrane depolarization in cultured telocytes, upregulated the expression of CX43 and ß-catenin, and downregulated the expressions of TRPV4 and TRPV1. Here, telocytes were identified in the vascular adventitia and intima, endocardium, myocardium, adventitia, and heart valves. Moreover, telocytes were broadly dispersed around cardiac vessels and interacted directly through gap junctions and indirectly through extracellular vesicles. Together, cardiac telocytes interact with berberine and then deliver drug information to the heart. Telocytes may be an essential cellular target for drug therapy of the cardiovascular system.

Tembusu virus induced apoptosis in vacuolate spermatogenic cells is mediated by Cytc-mediated mitochondrial apoptotic signaling pathway.

Duck Tembusu virus (DTMUV) is an emerging mosquito-borne flavivirus that infects mainly poultry and has caused huge economic losses to the poultry farming industry in China. Also known as duck hemorrhagic ovarian disease, DTMUV principally destroys ovarian tissue in ducks, causing a dramatic drop in egg production. and can also invade the male reproductive system causing lesions. Currently, little research has been done to reveal the underlying mechanisms of reproductive dysfunction in ducks caused by DTMUV infection. In this study, histopathological analysis and electron microscopy of testes of ducks infected with DTMUV showed that DTMUV caused testicular atrophy and cytoplasmic vacuolation in ducks. Terminal Deoxynucleotidyl Transferase-Mediated Nick-End Labeling (TUNEL) staining and real-time quantitative PCR(RT-qPCR) results further indicated that DTMUV induced spermatogenic cells apoptosis. After DTMUV infection, a large amount of cytochrome c(Cytc) was released from the mitochondrial matrix into the cytoplasm, activating downstream target proteins and causing apoptosis. To sum up, DTMUV induces spermatogenic cell apoptosis through the Cytc-induced mitochondrial apoptosis pathway, our study provides evidence for DTMUV infection-induced male reproductive disorders.

The Cellular Mechanism of Acupuncture for Ulcerative Colitis based on the Communication of Telocytes.

Acupuncture can ameliorate or treat diseases according to the meridian theory in traditional Chinese medicine (TCM); however, its mechanism has not been scientifically clarified. On the other hand, telocytes (TCs) are morphologically in accordance with the meridian system, which needs further cytological investigations and acupuncture confirmation. The present study showed that acupuncture could activate TCs in several ways, alleviating rabbit ulcerative colitis. TCs could cytologically communicate the acupoints, the acupuncture sites in skin with their corresponding large intestine by TC homo-cellular junctions, exosomes around TCs, and TC-mediated nerves or blood vessels. TCs expressed transient receptor potential vanilloid type 4, the mechanosensitive channel protein that can transduce the mechanical stimulation of acupuncture into biochemical signals transferring along the extremely thin and long TCs. Collectively, a cellular mechanism diagram of acupuncture was concluded based on TC characteristics. Those results also confirmed the viewpoint that TCs were the key cells of meridian essence in TCM.

Cellular Evidence for Telocytes Mediating Electroacupuncture to Ameliorate Obesity in Mice.

Electroacupuncture has been generally applied to target obesity, the principle of which is based on the meridian in traditional Chinese medicine. Although Telocytes (TCs) have been reported as the potential essence of meridians, their specific role in the electroacupuncture treatment of obesity remains unclear. Thus, we investigated the cellular evidence for TC-mediated electroacupuncture to alleviate obesity. Mice were divided into three groups as follows: electroacupuncture group (EA), control group (CG), and normal group (NG). The present study showed that the weight of perirenal white adipose tissue (rWAT), the serum level of total cholesterol, and the low-density lipoprotein cholesterol were all significantly decreased after electroacupuncture. Ultrastructurally, the prolongations (telopodes, Tps) of TCs were in direct contact with adipocytes, and lipid droplets were distributed on the surface of Tps. The proportions of double-positive fluorescent areas of TCs (CD34 and PDGFRα) were significantly elevated with concomitant elongated Tps in EA mice, as compared to those in CG mice. The expression of Cx43 and CD63 (gap junction and exosome markers) was significantly enhanced. These characteristics facilitated the transmission of electroacupuncture stimulation from skin to rWAT. We conclude that electroacupuncture relieved obesity by activating TCs morphologically, upregulating the gap junctions between TCs, and increasing the exosomes around TCs.

Comparison of endocytosis pathways of Duck Tembusu virus in BHK-21 and duck embryo fibroblasts.

The Duck Tembusu virus (DTMUV) is a zoonotic flavivirus characterized by nonsuppurative encephalitis and decreasing egg production that has adversely affected the poultry industry. While the way of invasion of DTMUV into different host cells, especially primary cells, remains elusive. In the present study, the ultrastructural pathological characteristics showed that DTMUV underwent a typical maturation and replication process: progeny virus particles gathered in rough endoplasmic reticulum (RER) cisternae, reached the cell membrane via Golgi body's endocrine channel, then were released in the infected baby hamster kidney-21 (BHK-21) and duck embryo fibroblast (DEF). Endoplasmic reticulum vesicles in BHK-21 were short rods and densely arranged like honeycombs, whereas vesicles in DEF were round and dispersed. Further study showed that the virus replication peak in mammalian BHK-21 cells was at 48 hpi, whereas in avian DEF cells was at 24 hpi. DTMUV entry into BHK-21 and DEF cells was blocked by clathrin inhibitor, chlorpromazine (CPZ), indicating that the flavivirus DTMUV enters BHK-21 and DEF both via a clathrin-mediated endocytosis (CME) pathway rather than caveola-mediated endocytosis or micropinocytosis. The endocytic difference in DTMUV entry into BHK-21 and DEF cells might provide insight into understanding the underlying virulence difference between passaged cells and cultured cells.

Tubson-2 decoction ameliorates rheumatoid arthritis complicated with osteoporosis in CIA rats involving isochlorogenic acid A regulating IL-17/MAPK pathway.

BACKGROUND: Osteoporosis (OP) is considered as one of the major comorbidities of rheumatoid arthritis (RA), and is responsible for fragility fracture. However, there is currently no effective treatment for RA complicated with OP. Tubson-2 decoction (TBD), a Mongolian medicine also known as Erwei Duzhong Decoction, has been shown to exert a preventive effect on post-menopausal osteoporosis (PMOP). The preventive effects of TBD on RA-induced OP, as well as the bioactive compound responsible and the underlying mechanisms, remain to be elucidated. OBJECTIVE: To explore the effects of TBD on RA-induced OP in vivo, and to elucidate the mechanism of isochlorogenic acid A (ICA), the effective component of TBD, in vitro. METHODS: To evaluate the anti-arthritic and anti-osteoporotic effects of TBD, we conducted H&E straining and safranine O/fast green, TEM, immunohistochemistry (IHC), bone histomorphometry, micro-CT imaging, and biomechanical testing in collagen induced arthritis (CIA) rats. The active ingredient in TBD was identified using network pharmacology and molecular docking. The identification was supported by in vivo IHC assay, and further confirmed using qRT-PCR, Western blot, and SEM analysis in TNF-α-treated MH7A cells and/or in LPS-exposed RAW264.7 cells. RESULTS: Oral administration of TBD attenuated the severity of arthritis and osteopenia as well as poor bone quality, in CIA rats. Additionally, TBD and the positive control, tripterygium glycosides (TG), exhibited similar effects in reducing inflammation in both the synovium and ankle joint. They also were both effective in improving bone loss, microarchitecture, and overall bone quality. TBD reduced the expression of MMP13, IL-17, and p-JNK protein in the synovium of CIA rats. ICA, which was screened, suppressed TNF-α or LPS-triggered inflammatory responses via down-regulating IL-17 signaling, involving in MMP13, IL-1ß, IL-23, and IL-17, and the MAPK pathway including p-ERK, p-JNK, and p-P38, both in MH7A cells and in RAW264.7 cells. Furthermore, ICA prevented osteoclasts from differentiating and bone resoprtion in a dose-dependent manner in vitro. CONCLUSION: This study provides the first evidence that TBD exerts intervening effects on RA-induced OP, possibly through the downregulation of the IL-17/MAPK signaling pathway by ICA. The findings of our study provides valuable insights for further research in this area.

Urinary Levels of 14 Metal Elements in General Population: A Region-Based Exploratory Study in China.

Metal pollution may lead to a variety of diseases; for this reason, it has become a matter of public concern worldwide. However, it is necessary to use biomonitoring approaches to assess the risks posed to human health by metals. In this study, the concentrations of 14 metal elements in 181 urine samples obtained from the general population of Gansu Province, China, were analyzed using inductively coupled plasma mass spectrometry. Eleven out of fourteen target elements had detection frequencies above 85%, namely, Cr, Ni, As, Se, Cd, Al, Fe, Cu and Rb. The concentrations of most metal elements in the urine of our subjects corresponded to the medium levels of subjects in other regional studies. Gender exerted a significant influence (p < 0.05) on the concentrations of Tl, Rb and Zn. The concentrations of Ni, As, Pb, Sr, Tl, Zn, Cu and Se showed significant differences among different age groups and the age-related concentration trends varied among these elements. There were significant differences in the urine concentrations of Zn and Sr between those subjects in the group who were frequently exposed to soil (exposed soil > 20 min/day) and those in the group who were not, indicating that people in regular contact with soil may be more exposed to metals. This study provides useful information for evaluating the levels of metal exposure among general populations.

Complete genomic analysis of rabbit rotavirus G3P[22] in China.

A rabbit rotavirus Z3171 isolate from diarrheic rabbits was identified and sequenced. The genotype constellation of Z3171 is G3-P[22]-I2-R3-C3-M3-A9-N2-T1-E3-H3, which is different from the constellation observed in previously characterized LRV strains. However, the genome of Z3171 differed substantially from those of the rabbit rotavirus strains N5 and Rab1404 in terms of both gene content and gene sequence. Our study suggests that either a reassortment event occurred between human and rabbit rotavirus strains or there are undetected genotypes circulating in the rabbit population. This is the first report of detection of a G3P[22] RVA strain in rabbits in China.

Foliar cadmium uptake, transfer, and redistribution in Chili: A comparison of foliar and root uptake, metabolomic, and contribution.

Atmospheric deposition is an essential cadmium (Cd) pollution source in agricultural ecosystems, entering crops via roots and leaves. In this study, atmospherically deposited Cd was simulated using cadmium sulfide nanoparticles (CdSN), and chili (Capsicum frutescens L.) was used to conduct a comparative foliar and root experiment. Root and foliar uptake significantly increased the Cd content of chili tissues as well as the subcellular Cd content. Scanning electron microscopy and high-resolution secondary ion mass spectrometry showed that Cd that entered the leaves via stomata was fixed in leaf cells, and the rest was mainly through phloem transport to the other organs. In leaf, stem, and root cell walls, Cd signal intensities were 47.4%, 72.2%, and 90.0%, respectively. Foliar Cd uptake significantly downregulated purine metabolism in leaves, whereas root Cd uptake inhibited stilbenoid, diarylheptanoid, and gingerol biosynthesis in roots. Root uptake contributed 90.4% Cd in fruits under simultaneous root and foliar uptake conditions attributed to xylem and phloem involvement in Cd translocation. Moreover, root uptake had a more significant effect on fruit metabolic pathways than foliar uptake. These findings are critical for choosing pollution control technologies and ensuring food security.

Ultrastructural study of the duck brain infected with duck Tembusu virus.

Duck Tembusu virus (DTMUV) is an emerging avian flavivirus characterized by causing severe ovaritis and neurological symptoms in ducks. The pathology of the central nervous system (CNS) caused by DTMUV is rarely studied. This study aimed to systematically investigate the ultrastructural pathology of the CNS of ducklings and adult ducks infected with DTMUV via transmission electron microscopy technology at a cytopathological level. The results showed that DTMUV caused extensive lesions in the brain parenchyma of ducklings and slight damage in adult ducks. The neuron was the target cell of DTMUV, and virions were mainly observed in their cisternae of rough endoplasmic reticulum and the saccules of Golgi apparatus. The neuron perikaryon showed degenerative changes where the membranous organelles gradually decomposed and disappeared with DTMUV infection. Besides neurons, DTMUV infection induced marked swelling in astrocytic foot processes in ducklings and evident myelin lesions in ducklings and adult ducks. The activated microglia were observed phagocytizing injured neurons, neuroglia cells, nerve fibers, and capillaries after the DTMUV infection. Affected brain microvascular endothelial cells were surrounded by edema and had increased pinocytotic vesicles and cytoplasmic lesions. In conclusion, the above results systematically describe the subcellular morphological changes of the CNS after DTMUV infection, providing an ultrastructural pathological research basis for DTMUV-induced neuropathy.

Multiple metal exposure and metabolic syndrome in elderly individuals: A case-control study in an active mining district, Northwest China.

The prevalence of metabolic syndrome (MetS) is increasing at an alarming rate worldwide, particularly among elderly individuals. Exposure to various metals has been linked to the development of MetS. However, limited studies have focused attention on the elderly population living in active mining districts. Participants with MetS (N = 292) were matched for age (±2 years old) and sex with a healthy subject (N = 292). We measured the serum levels of 14 metals in older people aged 65-85 years. Conditional logistic regression, restricted cubic spline model, multiple linear regression, and Bayesian Kernel Machine Regression (BKMR) were applied to estimate potential associations between multiple metals and the risk of MetS. Serum levels of Sb and Fe were significantly higher than the controls (0.58 µg/L vs 0.46 µg/L, 2167 µg/L vs 2042 µg/L, p < 0.05), while Mg was significantly lower (20035 µg/L vs 20,394 µg/L, p < 0.05). An increased risk of MetS was associated with higher serum Sb levels (adjusted odds ratio (OR) = 1.61 for the highest tertile vs. the lowest tertile, 95% CI = 1.08-2.40, p-trend = 0.018) and serum Fe levels (adjusted OR = 1.55 for the highest tertile, 95% CI = 1.04-2.33, p-trend = 0.032). Higher Mg levels in serum may have potential protective effects on the development of MetS (adjusted OR = 0.61 for the highest tertile, 95% CI = 0.41-0.91, p-trend = 0.013). A joint exposure analysis by the BKMR model revealed that the mixture of 12 metals (except Tl and Cd) was associated with increased risk of MetS. Our results indicated that exposure to Sb and Fe might increase the risk of MetS in an elderly population living in mining-intensive areas. Further work is needed to confirm the protective effect of Mg on MetS.

Heavy metal contamination and risk assessment in winter jujube (Ziziphus jujuba Mill. cv. Dongzao).

Winter jujube (Ziziphus jujuba Mill. cv. Dongzao) is a major fresh-eating jujube fruit with various important nutrients for humans. It can absorb heavy metals from polluted air, water and soils and applied pesticides, which may pose potential threats to consumers. Here, to evaluate the content of heavy metals in winter jujube and systematically evaluate the potential risks, we collected 212 winter jujube samples from four main producing areas in China and determined the contents of eight heavy metals (Cd, Cr, Pb, Ni, Cu, Zn, As, and Mn) using inductively coupled plasma mass spectrometer (ICP-MS). Based on the integrated pollution index (IPI) evaluation standard, more than 99.06% of samples were at safe levels. Moreover, clustering analysis divided the eight heavy metals into four groups, namely Cr/Ni, Cd/Pb, Cu/Mn/Zn, and As. Importantly, none of the analyzed heavy metals posed risks to adults as indicted by the average carcinogenic and non-carcinogenic risks. Notably, Cr and Cd could pose low carcinogenic risks to children (≤12 age group) when their concentration reached the 90th percentile. This study systematically assessed the health risks associated with heavy metal intake through winter jujube consumption and highlighted the necessity of constant heavy metal monitoring in winter jujube.

Isolation, culture, and characterization of duck primary neurons.

The duck is a representative and good model for studying the development and physiological mechanisms of the nervous system (NS) in waterfowl. Neurons are the basic structural and functional units of NS, but there is no detailed method for cultured duck neurons in vitro. An efficient and simple method for duck neuron culture is reported in this study. First, the sfigpecific markers (NSE and GFAP, respectively) were used to explore the timing of the development of neurons and astrocytes during the duck embryonic stage (E5-E18). The cytomorphology of tissues and cells was tracked with the microscope at different time points. The brain tissues from 10-day-old duck embryos were determined as the optimal sampling embryo age for neuron culture. Then, the brain tissue isolation method (papain digestion) and cell suspension inoculation density (7 × 105 cells/mL) were identified as the culture protocol to obtain target cells with high viability and high density. The purity of the cultured neurons was more than 95%. This experiment provides a supplement for the study of in vitro culture of waterfowl neurons and lays a good foundation for various subsequent studies.

Ultrastructural evidence of four types of lipofuscins in the melanomacrophagic centers in hepatocytes of zebrafish (Denio rerio).

Melanomacrophagic centers (MMCs) were studied in the hepatocytes of zebrafish using transmission electron microscope (TEM). The MMCs with irregular or amoeboid nucleus were located in the hepatocytes adjacent to the bile canaliculi. Several engulfed structures were present in the cytoplasm of MMCs. The most frequent observation was the presence of mitochondria, ranging in size from small to giant, with distorted shape and inconspicuous cristae. Occasionally the fragments of erythrocytes were found. The rough endoplasmic reticulum (rER) showed whirling around the mitochondria and lipid droplets, forming membrane-like structures. The damaged mitochondria were invaded by the lysosomes, and this was covered by a membrane led to the formation of lipofuscin. Four different types of lipofuscins were observed; namely, (1) granular with/without vacuoles of high electron-density, (2) homogenous surrounded by indistinct limiting membrane, (3) lamellated structures similar to inner matrix and cristae of mitochondria, and, (4) compound structure made by the combinations of first 3 types, (granular and homogenous, granular and lamellated, homogenous and lamellated). The present evidence suggests that MMCs in the hepatocytes of zebrafish perform continuous functions of removal of the damaged cellular organelles. The lipofuscin formation work in coordination with the cellular players of immune system and remove pathogens and maintain the internal homeostasis of cells.

Case Report: Successful therapy with all-trans retinoic acid combined with chemotherapy followed by hematopoietic stem cell transplantation for acute promyelocytic leukemia carrying the BCOR-RARA fusion gene.

Acute promyelocytic leukemia (APL) is characterized by the balanced translocation of chromosomes 15 and 17, resulting in the formation of PML-RARA fusion gene. More than 98% of APL have PML-RARA fusion, and less than 2% have other types of RARA gene partners, which named variant APL (vAPL). In the present study, we reported a vAPL with BCOR-RARA, which was the third case of BCOR-RARA APL published. The patient achieved complete remission (CR) with all-trans retinoic acid (ATRA) monotherapy, and molecular CR with ATRA plus standard chemotherapy. After that, he underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and ATRA maintenance and maintained a molecular CR status. This case provided valuable insights into the accurate identification of vAPL. Moreover, ATRA combined with chemotherapy followed by allo-HSCT was suggested as an optimal choice for those vAPL patients who had a high risk of relapse.

Duck Tembusu virus infection causes testicular atrophy.

In recent years, Duck Tembusu virus (DTMUV) is becoming an important emerging and re-emerging pathogen that severely harms the poultry industry in China. The DTMUV disease was principally identified by a sharp decline in egg production, whereas few studies were focused on the virus-reproductive system interaction, especially male reproductive system. Herein, the present study was aimed at investigating the in vivo morphological changes in testis from DTMUV-infected adult Shaoxing ducks. After DTMUV infection, the gross observation indicated that the testis of DTMUV-infected ducks was significantly atrophied at 2 days post-infection (dpi), 4 dpi, and 8 dpi. At microscopic and ultrastructural level, morphological analysis revealed that DTMUV could lead to cytoplasmic vacuolation and exfoliation in seminiferous epithelium, decrease in the diameter of seminiferous tubule (ST), and even induce interstitial inflammation in duck testis. Ulteriorly, the spermatogenic cells, especially spermatocytes, are identified as the target cells of DTMUV infection in the testis of ducks through immunohistochemistry (IHC). And more notably, single virus particles and clustered virus particles were observed in the spermatogenic cells from infected ducks. In summary, our results comprehensively illustrated the effects of DTMUV infection on the testis, the morphological changes underlying testicular atrophy and identified the target cells of DTMUV infection in the testis of ducks.

Dermal Microvascular Units in Domestic Pigs (Sus scrofa domestica): Role as Transdermal Passive Immune Channels.

The dermal microvascular unit (DMU) is a perivascular functional unit in the dermis. It is composed of microvascular and capillary lymphatics surrounded by immune cells. In this study, jet needle-free injection system was used to injected biocompatible carbon nanoparticles into the cervical skin of domestic pigs (Sus scrofa domestica) and assessed the morphological distribution of DMUs by hematoxylin erythrosine staining, immunohistochemistry (IHC), and transmission electron microscopy (TEM), and TEM was also used to observe the ultrastructural changes of DMUs after jet needle-free injection. Following our study, we identified DMUs in the dermis stratum papillare and similar structures in the dermis stratum reticulare, but the aggregation of CD68+ and CD1a+ cells in the dermis stratum papillare of DMUs by IHC confirmed that DMUs act as reservoirs of dermal immune cells, while similar structures in the dermis stratum reticulare should not be considered as DMUs. Ultrastructure of DMUs was revealed by TEM. Marvelous changes were found following xenobiotics attack, including the rearrangement of endothelial cells and pericytes, and the reactivity of immune cells. Novel interstitial cell telocyte (TC) was also identified around the microvasculature, which may have been previously known as the veil cell. Our results successfully identified the distribution of DMUs in the skin of domestic pigs, which might act as reservoirs of immune cells in the skin and play a role in immune surveillance and immune defense.