调节性T细胞和人类系统性红斑狼疮关系的研究进展

系统性红斑狼疮(SLE)是一种自身免疫系统疾病、可累及全身各个系统、脏器和组织,调节性T细胞(Tr)在其发生发展中发挥了重要的作用.目前所知的Tr具有免疫抑制的作用,包括两个亚群--CD4+Tr(CD4+CD25+Tr、Tr1和Th3细胞)和CD8+Tr(Ts细胞和CD8+CD25+T细胞).全面了解Tr和人类SLE的关系是在此领域发展新的免疫学治疗方法的基础.     

Chirurgie der Lider und ableitenden Tränenwege

Zusammenfassung  Die Chirurgie der Lider und ableitenden Tr?nenwege stellen eines der Fundamente der operativen T?tigkeit des Augenarztes in unserer Zeit dar. Auf diese Eingriffe darf und sollte unser Fach nicht verzichten. Da Lernen im freien Europa nicht verboten ist, sollten junge Operateure sich ermutigt fühlen, in den Zentren zu hospitieren, in denen diese Eingriffe mit Intensit?t und Nachdruck praktiziert werden.      

欧洲两地和中国西南山区飞蓬挥发油成份的比较

目的：阐明生态环境对飞蓬属植物挥发油成份的影响。方法：采用飞质联用法检测Erigeron acer L,挥发油成份。结果：共鉴定出59个化合物,欧洲两地产飞蓬挥发油的化学组成几乎相同,主要成份都是反式-罗斯烯α-金合欢烯、母菊酯、lachnophyllun ester 2-β-蒎烯和反式-β-金合欢烯,其余成份和含量也基本相近,而中国产飞蓬挥发油的主成份为lachnophyllun ester、β-石竹烯和橙花醛,而母菊酯、反式-罗革烯、反式-β-金合欢烯和α-金合欢烯含量很低或未检出。结论：中国与欧洲出产的飞蓬在挥发油成份上有很大差别。生长环境是影响本属植物挥发油成份的得要因素之一。     

Responses of CD4(+) CD25(+) Foxp3(+) and IL-10-secreting type I T regulatory cells to cluster-specific immunotherapy for allergic rhinitis in children

We investigated the effects of cluster specific immunotherapy (SIT) with Dermatophagoides pteronyssinus (Der p) on CD4(+) CD25(+) Foxp3(+) Treg cells and IL-10-secreting type I T regulatory (Tr1) cells in Der p-sensitized children with allergic rhinitis (AR). We performed a prospective randomized study involving 46 children (aged 8-13 yr), of whom 25 children received Der p-SIT + pharmacotherapy and 21 received only pharmacotherapy, over a period of 1 yr. Prior to and at end of treatment, CD4(+) CD25(+) Foxp3(+) Treg cells and allergen-specific IL-10(+) IL-4(-) , IFN-γ(+) IL-4(-) , and IL-4(+) IFN-γ-CD4(+) T cells were measured by flow cytometry. Similarly, IL-4, IFN-γ, and IL-10 in supernatants from allergen-stimulated peripheral blood mononuclear cell (PBMC) cultures were measured by ELISA, and the suppressive effect of CD4(+) CD25(high) T cells on cell proliferation and cytokine release was estimated from both groups. Allergen-specific serum IgE and IgG4 were also assessed at the beginning and end of treatment by RAST and ELISA, respectively. The levels of allergen-specific Tr1 cells, IgG4, and allergen-induced IL-10 synthesis from PBMC cultures were significantly increased after SIT for 1 yr compared with baseline levels (p < 0.001 for all), with significant correlation between increased levels of Tr1 cells and improvements in nasal symptoms (r = 0.48, p < 0.05). In contrast, the levels of CD4(+) CD25(+) Foxp3(+) T cells, allergen-specific Th1 and Th2 cells, the production of IL-4 and IFN-γ, and the function of CD4(+) CD25(high) T cells were not altered in either group at the end of treatment. These data suggest that the up-regulation of Tr1 cells may play an important role in SIT and be a useful marker of successful SIT in AR patients.     

The treatment of jaundice with medicinal plants in indigenous communities of the Sub-Himalayan region of Uttarakhand, India

Ethnopharmacological relevance

Inspite of tremendous advances made in allopathic medical practices, herbs still play an important role in the management of various liver diseases. A large number of plants and formulations have been claimed to have hepatoprotective activity. Jaundice is a symptom, indicative of the malfunctioning of the liver. This paper provides ethnomedicinal information on the plants used to treat jaundice by three important indigenous communities, i.e., nomadic Gujjars, Tharu and Bhoxa of Sub-Himalayan region, Uttarakhand, India.

Aims of the study

To record herbal preparations used by the studied indigenous communities in treatment of jaundice and discuss hepatoprotective properties of the recorded plants.

Research strategy and methods

The traditional knowledge of the studied indigenous communities on herbal preparations used for treating jaundice was collected through structured questionnaire and personal interviews. The interviews were conducted with 91 traditional healers (29 Bhoxa, 35 Tharu and 27 nomadic Gujjars) in Sub-Himalayan region of Uttarakhand, India. More than 250 research papers reporting ethnomedicinal information on the hepatoprotective plants used by various communities from different parts of India were extensively reviewed.

Results

A total of 40 medicinal plants belonging to 31 families and 38 genera were recorded to be used by the studied communities in 45 formulations as a remedy of jaundice. Bhoxa, nomadic Gujjars and Tharu communities used 15, 23 and 9 plants, respectively. To our knowledge eight plants reported in the present survey viz., Amaranthus spinosus L., Cissampelos pareira L., Ehretia laevis Roxb., Holarrhena pubescens Wall., Ocimum americanum L., Physalis divaricata D. Don, Solanum incanum L. and Trichosanthes cucumerina L. have not been reported earlier as remedy of jaundice in India. Literature review revealed that a total of 214 (belonging to 181 genus and 78 families), 19 (belonging to 18 genus and 12 families) and 14 (belonging to 14 genus and 11 families) plant species are used as internal, external and magico-religious remedies for jaundice, respectively by various communities in different parts of India. Most widely used hepatoprotective plant species for treatment of jaundice in India is Boerhavia diffusa L. followed by Tinospora cordifolia (Willd.) Miers, Saccharum officinarum L., Phyllanthus amarus Schumach. &; Thonn., Ricinus communis L., Andrographis paniculata (Burm. f.) Nees., Oroxylum indicum (L.) Kurz, Lawsonia inermis L. and Eclipta prostrata (L.) L.

Conclusions

The plants recorded in the present survey have also been discussed in relation to pharmacological studies and hepatoprotective phytoconstituents present in them. Most of the recorded plants have shown hepatoprotective effects on experimental animals in earlier studies but more studies are needed to assess hepatoprotective properties of some recorded medicinal plants viz., Averrhoa carambola L., Ehretia laevis Roxb., Holarrhena pubescens Wall., Mangifera indica L., Ocimum americanum L., Oroxylum indicum (L.) Kurz, Physalis divaricata D. Don, Solanum incanum L., Sphaeranthus senegalensis DC. and Tribulus terrestris L.. The plants enumerated in this study with high number of citations and wider distributions have given some useful leads for further biomedical research. Nevertheless more phytochemical, pharmaceutical and clinical studies are needed to evaluate hepatoprotective properties, efficacy and safety of all the claimed medicinal plants.     

Quantifying immunoregulation by autoantigen-specific T-regulatory type 1 cells in mice with simultaneous hepatic and extra-hepatic autoimmune disorders

Nanoparticles (NPs) displaying autoimmune disease-relevant peptide-major histocompatibility complex class II molecules (pMHCII-NPs) trigger cognate T-regulatory type 1 (Tr1)-cell formation and expansion, capable of reversing organ-specific autoimmune responses. These pMHCII-NPs that display epitopes from mitochondrial protein can blunt the progression of both autoimmune hepatitis (AIH) and experimental autoimmune encephalomyelitis (EAE) in mice carrying either disease. However, with co-morbid mice having both diseases, these pMHCII-NPs selectively treat AIH. In contrast, pMHCII-NPs displaying central nervous system (CNS)-specific epitopes can efficiently treat CNS autoimmunity, both in the absence and presence of AIH, without having any effects on the progression of the latter. Here, we develop a compartmentalized population model of T-cells in co-morbid mice to identify the mechanisms by which Tr1 cells mediate organ-specific immunoregulation. We perform time-series simulations and bifurcation analyses to study how varying physiological parameters, including local cognate antigenic load and rates of Tr1-cell recruitment and retention, affect T-cell allocation and Tr1-mediated immunoregulation. Various regimes of behaviour, including ‘competitive autoimmunity’ where pMHCII-NP-treatment fails against both diseases, are identified and compared with experimental observations. Our results reveal that a transient delay in Tr1-cell recruitment to the CNS, resulting from inflammation-dependent Tr1-cell allocation, accounts for the liver-centric effects of AIH-specific pMHCII-NPs in co-morbid mice as compared with mice exclusively having EAE. They also suggest that cognate autoantigen expression and local Tr1-cell retention are key determinants of effective regulatory-cell function. These results thus provide new insights into the rules that govern Tr1-cell recruitment and their autoregulatory function.     

Malignant acanthosis nigricans with Leser–Trélat sign and tripe palms: A case report

BACKGROUNDAcanthosis nigricans (AN), Leser–Trélat sign, and tripe palm are all skin diseases. To date, reports of these appearing as a paraneoplastic syndrome in a gastric cancer patient are quite rare.CASE SUMMARYWe report the case of a 61-year-old man with darkened skin color in the face and torso with no obvious inducement after 1 year of treatment for Riehl’s melanosis. He had 40 brown maculopapular eruptions on his face and the top of his head with obvious itching. Papillary wart-like hyperkeratosis with dark brown pigmentation was also observed on both sides of the areola. He had papilloma-like lesions on the face, around the orbit, and on the neck. His bilateral palms had small, smooth, papillary projections with millet-like appearance. Histopathological examination of the skin showed that the patient was suffering from AN, tripe palms, and Leser–Trélat sign. Gastroscopy showed the patient’s cardia was affected, and pathological biopsy revealed that he had moderate-to-poorly differentiated adenocarcinoma. Computed tomography test results showed that his cardia wall had thickened. Based on these histological and skin characteristics, the patient was diagnosed with gastric cancer with AN, tripe palms, and Leser–Trélat sign.CONCLUSIONResearchers should follow up on patients with malignant AN, Leser–Trélat sign, and tripe palms.     

The effects of particulate matter on atopic dermatitis symptoms are influenced by weather type: Application of spatial synoptic classification (SSC)

The effects of weather and air pollution on atopic dermatitis (AD) flares have not been well investigated. To investigate the effects of particulate matter (PM) on AD symptoms by weather type, a total of 125 young children (76 boys and 49 girls) under 6 years of age with AD living in Seoul, Korea, were enrolled as a panel and followed for 17 months between August 2013 and December 2014. AD symptoms were recorded on a daily basis, including itching, sleep disturbance, erythema, dry skin, oozing, and edema. Daily weather was classified into 7 categories according to spatial synoptic classification (SSC). Personal exposure to PM with an aerodynamic diameter less than 2.5 and 10?μm (PM_2.5 and PM₁₀, respectively) in each individual was estimated with time-weighted average concentrations considering outdoor and indoor levels of PMs and time to spend outdoors or indoors in a day. Generalized linear mixed models were used to analyze the effects of PM_2.5 and PM₁₀ on AD symptoms, controlling for ambient temperature, humidity, age, sex, SCORAD (SCORing of AD) at enrollment, fever, day of week, and topical corticosteroid use. A total of 20,168 person-days of symptom records were collected. The presence of AD symptoms was higher on dry polar (DP) days (45.4%, P?<?.0001) than on moist tropical (MT) days (37.7%, P < .0001). Overall, the risk of AD symptoms significantly increased with increased exposure to PM_2.5 and PM₁₀. Among the 7 weather types, the risks of AD symptoms caused by PM_2.5 and PM₁₀ exposure were significantly increased on dry moderate (DM) days, while not significant on the other weather types. In addition, lagged effect of PM_2.5 up to 4 days was found on DM days. In conclusion, dry moderate weather type, particulate matters, and their modifying effects should be simultaneously considered for proper management of AD.     

Regulatory T cells in autoimmune neuroinflammation

Regulatory T cells are the central element for the maintenance of peripheral tolerance. Several subtypes of regulatory T (Treg) cells have been described, and most of them belong to the CD4⁺ T-helper (Th) cell lineage. These specific subtypes can be discriminated according to phenotype and function. Forkhead box protein 3 (FoxP3)-expressing natural Treg cells (Tregs) and IL-10-producing, T-regulatory type 1 cells (Tr1) are the best-studied types of CD4⁺ regulatory T cells in humans and experimental animal models. It was shown that they play a crucial role during autoimmune neuroinflammation. Both cells types seem to be particularly important for multiple sclerosis (MS). Here, we discuss the role of CD4⁺ regulatory T cells in autoimmune neuroinflammation with an emphasis on Tregs and Tr1 cells in MS.