-
Cell cycle (Georgetown, Tex.) 03/2013; 12(7). · 5.36 Impact Factor
-
Yu-Ling Shi,
Matthew Weiland,
Jia Li,
Iltefat Hamzavi,
Marsha Henderson,
Richard H Huggins,
Bassel H Mahmoud,
Oma Agbai,
Xiaofan Mi,
Zheng Dong,
Henry W Lim,
Qing-Sheng Mi, Li Zhou
[show abstract]
[hide abstract]
ABSTRACT: Autoimmunity is the most accepted hypothesis to explain the pathogenesis of non-segmental vitiligo (NSV) (Le Poole and Luiten, 2008). Recent GWAS studies have identified vitiligo susceptibility genes that are related to immune regulation and immune targeting of melanocytes (Spritz, 2012). We (Zhou et al., 2012) and others (Ben Ahmed et al., 2012; Klarquist et al., 2010) recently reported that NSV patients have number and function defects in invariant natural killer T cells and CD4+ CD25+ Foxp3+ regulatory T cells, which further supports this theory. However, the exact molecular mechanisms are still unclear. © 2013 John Wiley & Sons A/S.
Pigment Cell & Melanoma Research 03/2013; · 5.06 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Immunosenescence is a result of progressive decline in immune system function with advancing age. Epidermal Langerhans cells (LCs), belonging to the dendritic cell (DC) family, act as sentinels to play key roles in the skin immune responses. However, it has not been fully elucidated how aging affects development and function of LCs. Here, we systemically analyzed LC development and function during the aging process in C57BL/6J mice, and performed global microRNA (miRNA) gene expression profiles in aged and young LCs. We found that the frequency and maturation of epidermal LCs were significantly reduced in aged mice starting at 12 months of age, while the Langerin expression and ability to phagocytose Dextran in aged LCs were increased compared to LCs from < 6 month old mice. The migration of LCs to draining lymph nodes was comparable between aged and young mice. Functionally, aged LCs were impaired in their capacity to induce OVA-specific CD4+ and CD8+ T cell proliferation. Furthermore, the expression of miRNAs in aged epidermal LCs showed a distinct profile compared to young LCs. Most interestingly, aging-regulated miRNAs potentially target TGF-β-dependent and non- TGF-β-dependent signal pathways related to LCs. Overall, our data suggests that aging affects LCs development and function, and that age-regulated miRNAs may contribute to the LC developmental and functional changes in aging.
Aging 11/2012; · 5.13 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Langerhans cells (LCs) are skin-residential dendritic cells that regulate skin immunity. MicroRNAs (miRNAs) are key regulators in the control of biological functions in a variety of cell types. Deletion of all miRNAs interrupts the homeostasis and function of epidermal LCs. However, the roles of individual miRNAs in regulating LC development and function are still completely unknown. MiRNA miR-233 is especially expressed in the myeloid compartment. Here, we reported that miR-223 is highly expressed in freshly isolated epidermal LCs, and tested whether miR-223 regulates LC development and function using miR-223 knockout (KO) mice. We found that the number, maturation, migration and phagocytic capacity of LCs were comparable between miR-223KO and wild-type mice. However, lack of miR-223 significantly increases LCs-mediated antigen-specific CD8(+) T cell proliferation in vivo and in vitro, while LCs from KO and WT mice showed comparable stimulation for antigen-specific CD4(+) T cells. Our data suggest that miR-223 negatively regulates LC cross-presentation, but may not be required for normal LC homeostasis and development.
The international journal of biochemistry & cell biology 11/2012; · 4.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that repress target genes at post-transcriptional level. Langerhans cells (LCs) are skin-residential dendritic cells (DCs) with a life cycle distinct from other types of DCs. miRNA deficiency interrupts the homoeostasis and function of epidermal LCs, suggesting the critical roles of miRNAs in LC development and function. However, the roles of individual miRNAs in regulating LC development and function remain completely unknown. MiRNA miR-150 is highly expressed in mature lymphocytes and regulates T- and B-cell development and function. Here, we reported that miR-150 is also expressed in epidermal LCs, and its expression is significantly down-regulated during in vitro LC maturation. Using a miR-150 knockout mouse model, we found that lack of miR-150 reduces the capacity of LCs to cross-present a soluble antigen to antigen-specific CD8(+) T cells, but does not disturb the development, maturation, migration and phagocytic capacity of LCs. Thus, our data indicate that miR-150 is required for LC cross-presentation.
Experimental Dermatology 11/2012; 21(11):876-7. · 3.54 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The highly conserved RNAs, microRNAs (miRNAs), are a class of small single stranded noncoding RNAs that function through translational repression of specific target mRNAs. miRNAs exhibit a wide range of involvement regulating gene expressions. miRNA expression dysregulated in cancer cells and damaged tissues from different diseases implicates a functional role of miRNAs in the disease development. More recently miRNAs have been detected in cell-free serum, and these circulating miRNAs can distinguish diseased individuals from healthy controls. The noninvasive nature of circulating miRNA collection and their sensitivity and specificity in diseases has encouraged a pursuit of miRNA biomarker research. As a result, approximately 100 circulating miRNAs have been identified as biomarkers for different diseases, and the number is growing. Here we review recently reported circulating miRNA biomarkers and discuss their values and challenges for the disease biomarkers.
RNA biology 06/2012; 9(6):850-9. · 5.56 Impact Factor
-
Li Zhou,
Kai Li,
Yu-Ling Shi,
Iltefat Hamzavi,
Tian-Wen Gao,
Marsha Henderson,
Richard H Huggins,
Oma Agbai,
Bassel Mahmoud,
Xiaofan Mi,
Henry W Lim,
Qing-Sheng Mi
[show abstract]
[hide abstract]
ABSTRACT: Although it is widely believed that non-segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, a clear understanding of defects in immune tolerance, which mediate this uncontrolled self-reactivity, is still lacking. In the present study, we systemically evaluated circulating regulatory T (Treg) cells, including CD4(+) CD25(+) FoxP3(+) Treg cells and invariant natural killer T (iNKT) cells, as well as naïve and memory CD4(+) and CD8(+) T cells and their cytokine production, in a cohort of 43 progressive NSV patients with race-, gender-, and age-matched healthy controls. We found that the general immunophenotypes of CD4(+) and CD8(+) T cells and the percentage of CD4(+) CD25(+) FoxP3(+) Tregs were comparable between NSV and healthy controls. However, percentages of peripheral iNKT cells were significantly decreased in NSV patients compared to that in healthy controls. Our data confirm the previous notion that the percentage of peripheral CD4(+) CD25(+) FoxP3(+) Tregs remains unaltered in NSV and suggests the involvement of defective iNKT cells in the pathogenesis of NSV.
Pigment Cell & Melanoma Research 05/2012; 25(5):602-11. · 5.06 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: CD1d-restricted Vα14 invariant NKT (iNKT) cells play an important role in the regulation of diverse immune responses. MicroRNA-mediated RNA interference is emerging as a crucial regulatory mechanism in the control of iNKT cell differentiation and function. Yet, roles of specific microRNAs in the development and function of iNKT cells remain to be further addressed. In this study, we identified the gradually increased expression of microRNA-150 (miR-150) during the maturation of iNKT cells in thymus. Using miR-150 knockout (KO) mice, we found that miR-150 deletion resulted in an interruption of iNKT cell final maturation in both thymus and periphery. Upon activation, iNKT cells from miR-150KO mice showed significantly increased IFN-γ production compared with wild-type iNKT cells. Bone marrow-transferring experiments demonstrated the cell-intrinsic characteristics of iNKT cell maturation and functional defects in mice lacking miR-150. Furthermore, miR-150 target c-Myb was significantly upregulated in miR-150KO iNKT cells, which potentially contribute to iNKT cell defects in miR-150KO mice. Our data define a specific role of miR-150 in the development and function of iNKT cells.
The Journal of Immunology 03/2012; 188(5):2118-26. · 5.79 Impact Factor
-
Journal of dermatological science 02/2012; 65(2):152-5. · 3.71 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: MicroRNAs (miRNAs) are recently discovered small non-coding RNAs and can serve as serum biomarkers for disease diagnosis and prognoses. Lack of reliable serum miRNA endogenous references for normalization in miRNA gene expression makes single miRNA assays inaccurate. Using TaqMan® real-time PCR miRNA arrays with a global gene expression normalization strategy, we have analyzed serum miRNA expression profiles of 20 female mice of NOD/ShiLtJ (n = 8), NOR/LtJ (n = 6), and C57BL/6J (n = 6) at different ages and disease conditions. We identified five miRNAs, miR-146a, miR-16, miR-195, miR-30e and miR-744, to be stably expressed in all strains, which could serve as mouse serum miRNA endogenous references for single assay experiments.
PLoS ONE 01/2012; 7(2):e31278. · 4.09 Impact Factor
-
Hepatology 12/2011; 55(5):1640-2; author reply 1642-3. · 11.66 Impact Factor
-
Acta Diabetologica 10/2011; · 2.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: MicroRNAs (miRNAs) are an abundant class of evolutionarily conserved, small, non-coding RNAs that post-transcriptionally regulate expression of their target genes. Emerging evidence indicates that miRNAs are important regulators that control the development, differentiation and function of different immune cells. Both CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells and invariant natural killer T (iNKT) cells are critical for immune homeostasis and play a pivotal role in the maintenance of self-tolerance and immunity. Here, we review the important roles of miRNAs in the development and function of iNKT and Treg cells.
Cellular & molecular immunology 08/2011; 8(5):380-7. · 2.99 Impact Factor
-
Rui-Qun Qi,
Li He,
Song Zheng,
Yuxiao Hong,
Lei Ma,
Shifa Zhang,
Liping Zhao,
Xinjian Guo,
Yong Wang,
Jiang-Yun Yu, [......], Li Zhou,
Qingsheng Mi,
Matthew Weiland,
John Z S Chen,
S S Salum McHenga,
Ya-Kun Wang,
Uwesu McHepange,
Zhimin Wang,
Hong-Duo Chen,
Xing-Hua Gao
[show abstract]
[hide abstract]
ABSTRACT: Frequent somatic mutations of BRAF (v-raf murine sarcoma viral oncogene homolog B) exon T1799A, which are implicated in the initial events of promutagenic cellular proliferation, are detected in both malignant melanomas (MM) and melanocytic nevi (MN). Most of the data regarding BRAF exon T1799A mutation have been from Caucasian cohorts, and a comprehensive screening of a homogeneous population is lacking. A total of 379 cases of MN and 195 cases of MM were collected from Chinese Han living in three geographical regions in China, i.e., northeast, southwest, and northwest China. BRAF exon T1799A mutation was detected by PCR and sequencing from microdissected tumors. In all, 59.8% cases of MN harbored BRAF exon T1799A mutation. Samples from regions with high UV exposure had higher detection rates than regions with lower UV exposure (73.5, 67.0, and 38.9%, respectively; χ(2) = 31.674, P = 1.59E-7). There were no differences in mutation rates between congenital and acquired MN; however, acquired MN with advanced age of onset had a higher mutation rate than those with younger age of onset (χ(2) = 13.23, P = 0.02). In all, 15.0% cases of MM harbored the BRAF mutation. The mutation rate in MM was not affected by region, histological type, gender, pattern of UV exposure, and age. The study suggests that the mutation is not necessarily associated with malignant transformation.
Journal of Investigative Dermatology 02/2011; 131(5):1129-38. · 6.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: microRNAs (miRNAs) are small noncoding RNAs that mediate RNA interference to suppress protein expression at the translational level. Accumulated evidence indicates that miRNAs play critical roles in various biological processes and disease development, including autoimmune diseases. Invariant natural killer T (iNKT) cells are an unusual CD1d-restricted subset of thymus-derived T cells that are potent regulators of diverse immune responses. Our previous studies with the mouse model of bone marrow-specific Dicer deletion suggest the involvement of Dicer-dependent miRNAs in the development and function of iNKT cells. In the present study, to further dissect the functional levels of Dicer-dependent miRNAs in regulating iNKT cell development, we generated a mouse model with the Dicer deletion in the thymus. Our data indicate that lack of miRNAs following the deletion of Dicer in the thymus severely interrupted the development and maturation of iNKT cells in the thymus and significantly decreased the number of iNKT cells in the peripheral immune organs. miRNA-deficient peripheral iNKT cells display profound defects in activation and cytokine production upon α-galactosylceramide (α-GalCer) stimulation. Our results demonstrate a critical role of the miRNA-dependent pathway in the thymus in the regulation of iNKT cell development and function.
Cellular & molecular immunology 11/2010; 7(6):447-53. · 2.99 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Invariant natural killer T (iNKT) cells, potent regulators of diverse immune responses, have been implicated in a number of diseases. The detailed mechanisms that drive iNKT cell development and maturation are still not completely understood. MicroRNAs (miRNAs) are small noncoding RNAs that regulate vast networks of genes that share miRNA target sequences. Our previous studies indicate that Dicer-dependent miRNAs play important roles in iNKT cell development, maturation, and function, but the roles of specific single miRNAs in this context are still lacking. Accumulated studies indicated that the miRNA miR-223 is a myeloid-specific miRNA. Here we report that miR-223 is highly expressed in thymic immature and activated splenic iNKT cells. To identify the role of miR-223 in iNKT cell development and function, miRNA-223-deficient mice were used. We have found that miR-223 deletion does not significantly interrupt iNKT cell development in the thymus, and miR-223-deficient mice have a normal frequency and number of iNKT cells in the thymus and peripheral immune organs. Furthermore, cytokine production of iNKT cells activated in vivo and in vitro shows no significant differences between miR-223 deficient mice and wild-type control. Thus, our data suggest that miR-223 may not be required for iNKT cell development and function.
International immunopharmacology 11/2010; 11(5):561-8. · 2.21 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related hormones such as leptin may be able to reverse muscle atrophy and alter the expression of atrophy-related miRNAs in aging skeletal muscle.
Biochemical and Biophysical Research Communications 09/2010; 400(3):379-83. · 2.48 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent studies have demonstrated that gene expression is regulated not only by protein-coding genes, but also by nonprotein-coding small RNA molecules, microRNAs (miRNAs). miRNAs have emerged as important regulators involved in many biological processes, including cell proliferation and differentiation, apoptosis and metabolism and disease development. Here we report that specific miRNA deficiency in pancreatic islet cells exacerbates multiple low-dose streptozotocin-induced murine autoimmune type 1 diabetes, suggesting that miRNAs expressed in islet beta cells regulate their susceptibility to immune-mediated beta cell destruction.
Cell cycle (Georgetown, Tex.) 08/2010; 9(15):3127-9. · 5.36 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: MicroRNAs are small noncoding RNAs that are produced endogenously and have emerged as important regulators in pathophysiological conditions such as development and tumorigenesis. Very little is known about the regulation of microRNAs in renal diseases, including acute kidney injury (AKI). In this study, we examined the regulation of microRNA-34a (miR-34a) in experimental models of cisplatin-induced AKI and nephrotoxicity. By Northern blot and real-time polymerase chain reaction analyses, we detected an induction of miR-34a in vitro during cisplatin treatment of mouse proximal tubular cells and also in vivo during cisplatin nephrotoxicity in C57BL/6 mice. In cultured cells, miR-34a was induced within a few hours. In mice, miR-34a induction was detectable in renal tissues after 1 d of cisplatin treatment and increased to approximately four-fold of control at d 3. During cisplatin treatment, p53 was activated. Inhibition of p53 with pifithrin-α abrogated the induction of miR-34a during cisplatin treatment of proximal tubular cells. In vivo, miR-34a induction by cisplatin was abrogated in p53-deficient mice, a result that further confirms a role for p53 in miR-34a induction during cisplatin nephrotoxicity. Functionally, antagonism of miR-34a with specific antisense oligonucleotides increased cell death during cisplatin treatment. Collectively, the results suggest that miR-34a is induced via p53 during cisplatin nephrotoxicity and may play a cytoprotective role for cell survival.
Molecular Medicine 04/2010; 16(9-10):409-16. · 3.76 Impact Factor
-
Qing-Sheng Mi,
Sheng-Li Yan,
Zai-Zhao Wang,
Ke-Hong Ding,
Changgui Li,
Luan Wang, Li Zhou,
Yasuhiko Yamamoto,
Hiroshi Yamamoto,
Hiroshi Okamoto,
Carlos Isales
Cell cycle (Georgetown, Tex.) 12/2009; 8(24):4179-81. · 5.36 Impact Factor
