Asthma is a chronic disease of airway inflammation due to excessive T helper cell type 2 (Th2) response. Present treatment based on inhalation of synthetic glucocorticoids can only control Th2-driven chronic eosinophilic inflammation, but cannot change the immune tolerance of the body to external allergens. Regulatory T cells (Tregs) are the main negative regulatory cells of the immune response. Tregs play a great role in regulating allergic, autoimmune, graft-versus-host responses, and other immune responses. In this review, we will discuss the classification and biological characteristics, the established immunomodulatory mechanisms, and the characteristics of induced differentiation of Tregs. We will also discuss the progress of Tregs in the field of asthma. We believe that further studies on the regulatory mechanisms of Tregs will provide better treatments and control strategies for asthma.
Antigens, CD/analysis* ; Apyrase/analysis* ; Asthma/immunology* ; Cell Differentiation ; Cytokines/metabolism* ; Humans ; Lymphocyte Transfusion ; T-Lymphocytes, Regulatory/immunology*

PURPOSEMacrophages are known to be important for healing numerous injured tissues depending on their functional phenotypes in response to different stimuli. The objective of this study was to reveal macrophage phenotypic changes involved in exercise-induced skeletal muscle injury and regeneration.

METHODSAdult male Sprague-Dawley rats experienced one session of downhill running (16° decline, 16 m/min) for 90 min. After exercise the blood and soleus muscles were collected at 0 h, 6 h, 12 h, 1 d, 2 d, 3 d, 1 w and 2 w after exercise, separately.

RESULTSIt was showed that CD68 M1 macrophages mainly infiltrated into muscle necrotic sites at 1-3 d, while CD163 M2 macrophages were present in muscles from 0 h to 2 weeks after exercise. Using transmission electron microscopy, we observed activated satellite cells 1 d after exercise. Th1-associated transcripts of iNOS and Ccl2 were inhibited post exercise, while COX-2 mRNA was dramatically increased 12 h after running (p < 0.01). M2 phenotype marker Arg-1 increased 12 h and 3 d (p < 0.05, p < 0.01) after exercise, and Clec10a and Mrc2 were up-regulated in muscles 12 h following exercise (p < 0.05, p < 0.05).

CONCLUSIONThe data demonstrate the dynamic patterns of macrophage phenotype in skeletal muscle upon eccentric exercise stimuli, and M1 and M2 phenotypes perform different functions during exercise-induced skeletal muscle injury and recovery.

Animals ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Macrophages ; physiology ; Male ; Muscle, Skeletal ; injuries ; pathology ; Myoglobin ; blood ; Phenotype ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; analysis

OBJECTIVE: To investigate the charactcristics of CD180 expression and differentiation diagnostic value in B cell chronic lymphoproliferative disorders (B-CLPD) through detecting the mean fluorescence intensity（MFI）of CD180 in different sub types of B-CLPD，using multiparameter flow cytometry (FCM). METHODS: The CD180 MFI of malignant B cells in 178 patients with B-CLPD was detected by FCM. The level of CD180 MFI in various types of B-CLPD was compared to the normal control group. The level of CD180 MFI among sub-types of B-CLPD was also compared. RESULTS: (1) The expression levels of CD180 in B-CLPD was significantly lower as compared with the normal controls，except the spleen difuse red pulp lymphoma (SDRPL); (2) The CD180 MFI in chronic lymphocytic leukemia sCLL) was significantly lower as compared with other B-CLPD cells; (3) CD180 ware significantly overexpressed in HCL compared with MCL，LPL，and MZL (P <0.05); (4) In the spleen-derived B-CLPD，such as SMZL，HCL, HCL variation and SDRPL，the expression of CD180 has significant difference between lymphomas with or without villous. CONCLUSION Utilizing the multiparameter flow cytometry for defecting expression of CD180 and other immunological markers can more efficiently distinguish the subtypes of B-CLPD.
Antigens, CD ; analysis ; B-Lymphocytes ; Biomarkers ; Flow Cytometry ; Humans ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell ; Lymphoproliferative Disorders

OBJECTIVE: To identify differentially expressed genes in peripheral blood mononuclear cells between patients with continuous mild-to-moderate asthma and healthy controls using mRNA microarray in order to explore the underlying signaling pathways and clarify the roles of CD4+ T cells in the pathogenesis of asthma. METHODS: Global transcriptomic profiles of the CD4+ T cells were defined by using Agilent Sure Print G3 Human GE 8×60K microarray. Enrichment pathways were analyzed with Ingenuity Pathway Analysis (IPA) software. RESULTS: Compared with controls, 805 genes were up-regulated, 192 were down-regulated in asthma patients. Among these, the expression of 38 annotated genes have varied by 4 times or more. Expression of CD300A was inversely proportional to the absolute value of eosinophils (r=-0.89, P=0.02) as well as the proportion of eosinophils (r=-0.94, P=0.004), while CSF1R was inversely proportional to PD20 (r=-0.83, P=0.04) and AQLQ (r=-0.88, P=0.02) by correlation analysis. CONCLUSION Numerous pathophysiological pathways may be involved in the pathogenesis of asthma. Above findings have provided a basis for the delineation the pathogenesis of asthma.
Antigens, CD ; genetics ; Asthma ; immunology ; CD4-Positive T-Lymphocytes ; cytology ; Case-Control Studies ; Eosinophils ; Gene Expression Profiling ; Humans ; Leukocytes, Mononuclear ; Oligonucleotide Array Sequence Analysis ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor ; genetics ; Receptors, Immunologic ; genetics ; Transcriptome

OBJECTIVETo investigate the relationship between atrial fibrillation (AF) and serum soluble CD163.

METHODSA total of 336 patients with heart valve disease were included in this study, including 167 with AF and 169 with sinus rhythm. The clinical data were compared between the two grops, and Logistic regression analysis was used to identify the risk factors associated with AF.

RESULTSThe levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor (TNF), interleukin-6 (IL - 6), high-sensitivity C-reactive protein (hs-CRP) and left atrial diameter (LAD) all differed significantly between the two groups (P<0.05). Serum soluble CD163 levels in AF patients were significantly higher than those in patients with sinus rhythm (P<0.05). Serum soluble CD163 was positively correlated with TNF (r=0.244, P=0.244), IL-6 (r=0.186, P=0.186), hs-CRP (r=0.183, P=0.183) and LAD (r=0.194, P=0.194) in patients with AF. Logistic regression analysis showed that LAD, IL-6, TNF, hs-CRP and CD163 were all associated with AF. ROC curve analysis showed that the area under curve of serum soluble CD163 was 0.861 in patients with AF (CI 95%: 0.820-0.901, P<0.01) with a sensitivity and a specificity of 80.8 and 76.9%, respectively.

CONCLUSIONSerum soluble CD163 level may be a risk factor for AF, and an increased soluble CD163 level may indicate active inflammation in AF patients.

Antigens, CD ; blood ; Antigens, Differentiation, Myelomonocytic ; blood ; Atrial Fibrillation ; blood ; C-Reactive Protein ; analysis ; Heart Atria ; pathology ; Humans ; Inflammation ; blood ; Interleukin-6 ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Receptors, Cell Surface ; blood ; Risk Factors ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the gene mutation spectrum of β-thalassemia in Dai ethnic population of 2 border region in Chinese Yunnan Province.

METHODSThe patients with β-thalassemia in Dai ethnic population of Dehong and Xishuangbanna autonamic prefecture were screened by using blood routine detection and capillary electrophoresis. The β-globin gene mutation in patients with β-thalassemia were detected by using PCR reverse dot-blot hybridization (PCR-RDB), the constitutive rate of gene mutation in patients with β-thalassemia of Dai ethnic population in two border regions was analyzed and compared.

RESULTSA total of 186 patients with gene mutation of β-thalassemia were confirmed. Among them, 10 gene mutation were found, and the 5 main gene mutations were CD26 (62.56%), CD41-42 (18.97%), CD17 (14.36%), CD71-72 (2.05%) and IVS-II-654 (1.54%). Among Dai ethinic population in Dehong region, 4 gene mutations were found including CD26 (80.31%), CD17 (11.02%), CD41-42 (6.30%) and CD71-72 (2.36%). Among Dai ethinic population in Xishuangbanna region, 6 gene mutations were found, out of them the more common gene mutations were CD41-42 (42.64%), CD26 (29.41%) and CD17 (20.59%).

CONCLUSIONThe gene mutations of β-thalassemia in Dai ethinic population of Yunnan province has been confirmed to be more genetic heterogenicity, the spectrums of β-thalassemia mutations in Dai ethinic population of different regions were significant different.

Antigens, CD ; genetics ; Asian Continental Ancestry Group ; China ; DNA Mutational Analysis ; Electrophoresis, Capillary ; Ethnic Groups ; Genetic Therapy ; Humans ; Mutation ; Nucleic Acid Hybridization ; Polymerase Chain Reaction ; beta-Globins ; genetics ; beta-Thalassemia ; ethnology ; genetics

OBJECTIVETo investigate the diagnostic role of STAT6 immunohistochemistry in solitary fibrous tumors (SFT)/meningeal hemangiopericytomas (HPC).

METHODEvaluated the expression of STAT6, vimentin, CD34, EMA, PR, S-100, CD56, GFAP and Ki-67 in a cohort of 37 SFT/meningeal HPC, 30 meningiomas and 30 schwannomas by immunohistochemistry staining.

RESULTSAll SFT/meningeal HPC demonstrated nuclear positivity for STAT6, and the proportion of positive tumor cells ranged from 60% to 95%, with no significant difference cases.Vimentin was strongly positive in all cases. CD34, EMA and PR positivity was found in 32 cases, 1 case and 4 cases, respectively.S-100 protein, CD56 and GFAP were negative; Ki-67 labeling index was 1%-8%. However, the meningiomas and schwannomas were negative for STAT6.

CONCLUSIONSSTAT6 is a relatively specific biomarker for SFT/meningeal HPC, and may be used in the diagnosis and differential diagnosis of SFT/meningeal HPC, especially for the atypical cases, and allows the precise pathologic diagnosis of SFT/meningeal HPC.

Antigens, CD ; analysis ; Antigens, CD34 ; analysis ; Antigens, Differentiation, T-Lymphocyte ; analysis ; Biomarkers, Tumor ; analysis ; Diagnosis, Differential ; Glial Fibrillary Acidic Protein ; analysis ; Hemangiopericytoma ; chemistry ; diagnosis ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; analysis ; Meningeal Neoplasms ; chemistry ; diagnosis ; Meningioma ; chemistry ; diagnosis ; Neurilemmoma ; chemistry ; diagnosis ; S100 Proteins ; analysis ; STAT6 Transcription Factor ; analysis ; Solitary Fibrous Tumors ; chemistry ; diagnosis ; Vimentin ; analysis

OBJECTIVETo study the clinical manifestation, pathologic features and immunophenotype of histiocytic necrotizing lymphadenitis (HNL).

METHODSThe clinicopathologic data of 84 patients with HNL from 2005 to 2014 were retrospectively studied. Immunohistochemical staining using EliVision method for CD20, PAX5, CD3, CD45RO, CD4, CD8, CD56, CD68, CD123, granzyme-B, TIA1 and MPO was carried out. In-situ hybridization for Epstein-Barr virus RNA was performed on archival lymph node biopsy tissue.

RESULTSImmunohistochemical study showed that the lesional cells were predominantly histiocytes (CD68+), plasmacytoid dendritic cells (CD123+) and T lymphocytes (CD3+ and CD45RO+). Clusters of CD68-positive cells with strong and diffuse MPO expression were identified. T lymphocytes with CD4 and CD8 positivity were noted. CD56+ natural killer cells and CD20+/PAX5 B cells were rare. Apoptosis-related markers, including TIA1 and granzyme B were expressed by T lymphocytes and histiocytes in lymph nodes of HNL. In-situ hybridization for Epstein-Barr virus RNA was positive in only 10.0% of the cases.

CONCLUSIONSHNL shows no specific clinical and laboratory findings. Recognition of the characteristic histopathologic changes in lymph node biopsy of HNL is the key to correct diagnosis. Immunohistochemical study using a panel of markers, including CD3, CD4, CD8, MPO, CD123, granzyme-B and TIA1, is helpful in the differential diagnosis of HNL.

Antigens, CD ; analysis ; Biomarkers ; Dendritic Cells ; pathology ; Diagnosis, Differential ; Granzymes ; analysis ; Herpesvirus 4, Human ; genetics ; Histiocytes ; pathology ; Histiocytic Necrotizing Lymphadenitis ; complications ; immunology ; pathology ; virology ; Humans ; Immunohistochemistry ; Immunophenotyping ; In Situ Hybridization ; methods ; Lymph Nodes ; RNA, Viral ; analysis ; Retrospective Studies ; T-Lymphocytes ; immunology ; pathology

OBJECTIVETo study the clinical significance of CD163 in the diagnosis and the evaluation of severity and prognosis of childhood hemophagocytic lymphohistiocytosis (HLH).

METHODSNinety-four children were classified into Epstein-Barr virus (EBV)-positive (n=55) and EBV-negative groups (n=39; control group). The EBV-positive group was subgrouped into infectious mononucleosis (IM; n=47) and HLH (n=8). Serum levels of soluble CD163 were measured using ELISA. Expression of CD163 on mononuclear cells was detected by flow cytometry.

RESULTSThe serum levels of soluble CD163 were>10 000 ng/mL in all eight HLH patients (>30 000 ng/mL in 3 cases). The mean serum levels of soluble CD163 in the HLH group were significantly higher than in the control and IM groups (P<0.05). The serum levels of soluble CD163 in EBV-positive children were positively correlated with EBV-DNA copies and serum levels of ferritin and LDH, but were negatively correlated with white blood cell count, neutrophil count, hemoglobin and platelet count. The follow-up after treatment for three HLH patients showed that serum levels of soluble CD163 were significantly reduced, but the soluble CD163 levels rebounded in one patient who was complicated by fungal pneumonia infection.

CONCLUSIONSThe levels of serum soluble CD163 may be related to the severity in children with HLH. The EBV-positive children with soluble CD163 levels >10 000 ng/mL should be considered the possibility of HLH.

Adolescent ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Child ; Child, Preschool ; Epstein-Barr Virus Infections ; immunology ; Female ; Humans ; Infant ; Male ; Receptors, Cell Surface ; analysis

OBJECTIVETo construct the expression vector pLCK-CD69-IRES-EGFP that contains mouse cell surface activation protein CD69 and enhanced green fluorescent protein(EGFP),and to generate CD69 transgenic mice based on this vector.

METHODSFirst, RNA was extracted from mouse lung tissue and cDNA was synthesized via reverse transcription. PCR primer was designed through the PubMed searching, then mouse CD69 DNA fragment was amplified with PCR. Second, this DNA fragment was subcloned to the pInsulater-LCK-IRES-EGFP plasmid and constructed the transgenic vector after the verification of nucleotide sequence. Third, the expression vector was then transfected into 293 T cells and its expression in 293 T cells was observed under fluorescence microscope. Last, microinjection was performed to transfer the expression vector pLCK-CD69-IRES-EGFP into fertilized eggs, which were implanted into pseudo-pregnant recipient mice. After birth the tail samples of the pups were obtained for the purpose of genotyping to determine the transgenic founders. Fluorescence microscope and flow cytometer were used to measure the expression of CD69 on cells.

RESULTSThe construction of the expression vector pLCK-CD69-IRES-EGFP was verified by enzyme digestion and DNA sequencing. The transfected 293 T cell showed expression of the protein under fluorescence microscope. Identification of PCR for the tail tissue of the pups confirmed the present of CD69 transgene and resting lymphocytes demonstrated the expression of CD69.

CONCLUSIONThe construction of expression vector pLCK-CD69-IRES-EGFP and generation of CD69 transgenic mice have been successfully processed, which lays a foundation of the solid pattern studies in inflammatory diseases.

Animals ; Antigens, CD ; genetics ; Antigens, Differentiation, T-Lymphocyte ; genetics ; DNA, Complementary ; Genetic Vectors ; Genotype ; Green Fluorescent Proteins ; genetics ; Lectins, C-Type ; genetics ; Mice ; Mice, Transgenic ; Plasmids ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Transfection