A prospective multi-institutional study to verify the non-inferiority of postoperative pain in robot-assisted thoracic surgery in comparison with video-assisted thoracoscopic surgery for lung cancer: The Japanese RATS interest group 01 (J-RATSIG 01).

OBJECTIVES: We sought to compare the latest data on postoperative pain between robot-assisted thoracic surgery (RATS) and video-assisted thoracoscopic surgery (VATS), and to clarify the relationship between the number or placement of ports and postoperative pain in patients with lung cancer. METHODS: Patients who underwent anatomical lung resection by RATS or VATS and whose chest tube was removed within 7 days were enrolled. The primary endpoint was the percentage of patients with a numeric rating scale (NRS) score ≤ 3 on postoperative day 30 (POD30). The target sample size was 400 patients. RESULTS: Four hundred five patients (RATS, n = 196; VATS, n = 209) managed at 12 institutions were included. Ninety-nine patients in the VATS group underwent a uniport procedure. Significant differences were observed between the RATS and VATS groups in the mean number of inserted ports (5.0 vs. 2.2), number of injured intercostal sites (2.9 vs. 1.9), largest wound size (3.4 vs. 3.7 cm), operation time (202 vs. 165 min), and use of epidural anesthesia or continuous nerve block (45 vs. 31 %). In the RATS and VATS groups, the rates of NRS≤3 on POD30 were 82.0 % and 94.7 % (95 %CI: -19.0 to -6.6 %), respectively, which could not prove noninferiority. However, in a multivariable analysis, the RATS approach was not proven to be a significant risk factor. CONCLUSION: In the current status of minimally invasive thoracic surgery in Japan, RATS involves a greater number of ports, longer operation time, and higher frequency of local anesthesia than VATS and may be inferior in terms of postoperative pain.

Massive hemothorax in a pregnant patient with neurofibromatosis type 1.

BACKGROUND: Reports of spontaneous hemothorax in patients with neurofibromatosis type 1 are scarce despite the severe complication. We herein present the first case of hemothorax in a neurofibromatosis type 1 patient during pregnancy and discuss the difficulty associated with its diagnosis and treatment. CASE PRESENTATION: A 39-year-old female at 34 weeks gestation presented with sudden left back pain and dyspnea. Chest radiography revealed massive left pleural effusion. Computed tomography showed bleeding from the intercostal artery. Although the patient appeared hemodynamically stable, the fetus was in a critical condition. Emergency caesarean section was performed within 1 hour. Subsequently, we performed endovascular coil embolization of the intercostal artery. While this intensive treatment saved the patient, her fetus could not be rescued. CONCLUSIONS: Patients with neurofibromatosis type 1 may develop massive hemothorax without gross lesions. In late pregnancy, sufficient infusion and quick hemostasis are essential and can be lifesaving.

The impact of self-efficacy for physical activity on health-related quality of life in total knee arthroplasty recipients.

BACKGROUND: Some patients with end-stage osteoarthritis of the knee remain unsatisfied after total knee arthroplasty (TKA). We postulated that to increase satisfaction, self-efficacy (SE) for physical activity should receive more attention in rehabilitative intervention, alongside the management of patient expectations, pain, and function. OBJECTIVE: We examined the relative impact of Physical Activity SE on Health-Related Quality of Life (HRQOL) alongside other factors such as pain and physical function which are well-addressed by current interventions. METHODS: One hundred and six first-TKA recipients (15 Male/91 Female, age 73.6 ± 7.2) were evaluated at 3 and 6 months post-operatively using the Medical Outcomes Study 36-Item Health Survey (SF-36v2) for HRQOL, knee extension strength measurement, Timed Up and Go test (TUG), One Leg Standing time test (OLS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for pain and function, and an instrument for measuring Physical Activity SE among the frail elderly in Japan. RESULTS: Significant improvement over pre-operative values was found at 3 and 6 months in TUG, OLS, WOMAC Pain and Function, and the 8 subscales of the SF-36v2. Factors found to significantly impact SF-36v2 subscale scores at 6 months post-operatively were found to be knee pain, knee function, and SE for physical activity. CONCLUSION: These results support our postulation that interventions to improve SE for physical activity could have comparable impact alongside interventions for knee pain and knee function, on the advancement of HRQOL among TKA recipients.

Surgical fixation by mesh plate and intraoperative safe techniques for the manubrium sterni.

Plate osteosynthesis for oblique fracture of the manubrium sterni is quite rare. We present a case of a 37-year-old man with oblique fracture of the manubrium sterni caused by a traumatic injury. He was operated on using a variable-angle locking compression plate Mesh Plate 2.4/2.7 and had a good postoperative result. We also discuss intraoperative safe techniques such as use of a cement spatula for reduction support tools and depth-limited drilling to prevent excess drilling of the opposite cortex.

Evaluation of intra-tumoral blood feeding to predict the effect of induction therapy in patients with locally advanced lung cancer.

There is little known about predictors of the effects of induction therapy in locally advanced lung cancer, including superior sulcus tumors. We analyzed whether intra-tumoral blood feeding could predict a pathologic complete response (pCR). Patients who underwent induction therapy followed by surgery for locally advanced lung cancer were retrospectively reviewed. The intra-tumoral blood feeding was defined by the CT value (HU, Hounsfield unit), which was calculated by subtracting the non-enhanced value from the contrast-enhanced value (divided into the early and delayed phase) at the maximum diameter of the tumor on dynamic CT. The cases were classified, according to the efficacy of induction therapy, into the pCR and residual tumor (pRT) group. There were 38 cases of T3 and 12 of T4; the induction therapy consisted of chemoradiotherapy in 39 patients, chemotherapy in 6, and radiotherapy in 5. A pCR was obtained in 15 (30%) patients. The mean CT values of the early and delayed phases in the pCR group were 14.8 and 30.7 HU, while those in the pRT were 15.3 and 32.2 HU, respectively. A logistic regression analysis revealed that a smaller tumor size (< 42 mm) was a non-significant predictor of a pCR (p = 0.09); the maximum standardized uptake value on FDG-PET and the CT values on the early and delayed phases of dynamic CT were not associated with the achievement of a pCR. In conclusion, intra-tumoral blood feeding of the locally advanced lung cancer did not predict the effects of induction therapy, whereas smaller sized tumors tended to show a better response.

Verification of T descriptor with consolidation size for sub-centimeter non-small cell lung cancer.

PURPOSE: In the most recent (eighth) edition of the TNM classification, the clinical T descriptor has been adapted to measure the consolidation size of sub-solid lung cancer. Sub-centimeter non-small cell lung cancer (NSCLC) has thereby been subclassified into three groups: Tis, T1mi, and T1a; however, the revision has not been validated well. Thus, we investigated the clinicopathological characteristics and long-term oncological outcomes of sub-centimeter NSCLCs based on the solid size. METHODS: The subjects of this retrospective review were 99 patients who underwent complete resection for NSCLC with ≤ 1 cm in consolidation size on computed tomography (CT). Survival was reanalyzed after reclassification according to the new TNM classification. RESULTS: This cohort consisted of 14 patients with cTis tumors, 18 with cT1mi tumors, and 67 with cT1a tumors. Among the patients with tumors classified as cT1a, two had lymph node metastasis and two had vascular invasion. The cumulative incidences of recurrence at 5 and 10 years were 0% for cTis/cT1mi tumors, and 4.5% and 6.1% for cT1a tumors, respectively. CONCLUSIONS: There may be pathological and survival differences between cTis/cT1mi tumors and cT1a tumors, but not between cTis tumors and cT1mi tumors.

The tumor doubling time is a useful parameter for predicting the histological type of thymic epithelial tumors.

PURPOSE: We assessed the utility of the tumor doubling time (TDT) for predicting the histological type of thymic epithelial tumors. METHODS: We retrospectively reviewed 130 patients with thymic epithelial tumors who underwent computed tomography two or more times before surgery. The patients were divided into low-risk thymoma (types A, AB and B1), high-risk thymoma (types B2 and B3) and thymic carcinoma (thymic carcinoma and thymic neuroendocrine tumor) groups. In the 96 patients who showed tumor enlargement, the relationship between the histological type and the TDT of the tumor was investigated. RESULTS: The study population included 55 men and 41 women from 26 to 82 years of age. The TDT of the thymic carcinoma group (median 205 days) was significantly shorter in comparison to the low-risk thymoma (median 607 days) and high-risk thymoma (median 459 days) groups. No significant differences were observed between the low-risk thymoma and high-risk thymoma groups. When we set the cutoff time for differentiating thymic carcinoma group from thymoma at 313 days, the sensitivity and specificity were 83.8% and 82.1%, respectively. CONCLUSIONS: The TDT is a useful parameter for differentiating between thymoma and thymic carcinoma group.

Multimodality therapy for thymoma patients with pleural dissemination.

BACKGROUND: Although multidisciplinary treatment is recommended for patients with advanced stage and recurrent thymoma, a detailed treatment strategy remains controversial. We have performed a multimodality therapy of induction chemotherapy (CAMP therapy: cisplatin, doxorubicin, and methylprednisolone) combined with surgery for those patients. We now conducted a retrospective study for investigating the results of this multimodality therapy for thymoma patients with pleural dissemination. PATIENTS AND METHODS: Between 2003 and 2017, 201 patients underwent surgical resection for thymomas. Twenty-six of them received induction CAMP therapy followed by surgery, and 19 of them with pleural dissemination were enrolled in this study. Those cohort were divided into 2 groups by employing surgical procedures: extrapleural pneumonectomy (EPP) group (n = 10) and resection of plural dissemination (RPD) group (n = 9). RESULTS: The median age of all patients was 49 years. Based on the WHO classification, the histological diagnoses of those thymomas were as follows: Type B1 (n = 1), Type B2 (n = 13), and Type B3 (n = 5). Seven patients were complicated with myasthenia gravis (MG). Clinical stage of the 13 primary cases based on the Masaoka classification were stage IV, and the remaining six cases had recurrent pleural dissemination after surgery. Partial response in induction CAMP therapy was obtained in 78.9% (n = 15) of the patients. Adverse events (Grade 4) occurred in 2 patients (10.5%). Postoperative complications (Grade 4) were observed in 2 patients (10.5%). In all of the enrolled patients, the five-year overall survival rate (5Y-OS) and 5-year progression-free survival rate (5Y-PFS) were 76.7% and 55.1%, respectively. In the EPP group, 5Y-OS and 5Y-PFS were 83.3% and 83.3%, respectively, and in the RPD group, 70.0% and 29.6%, respectively. CONCLUSIONS: Multidisciplinary treatment using induction CAMP therapy and surgical resection for thymoma patients with pleural dissemination was effective and feasible. Because of the low recurrent rate of disease, young patients with good cardiopulmonary function and well-controlled MG might be good candidates for EPP.

Verification of the diagnostic strategy for anterior mediastinal tumors.

BACKGROUND: For thymic epithelial tumors (TETs), the National Comprehensive Cancer Network guideline has suggested that complete excision of the tumor should be performed without a preoperative biopsy when resectable. However, little evidence has been provided to support this strategy. The purpose of this study was to review our diagnostic process and to evaluate the validity of radical resection of anterior mediastinal masses (AMMs) without pathological confirmation. METHODS: A total of 254 patients underwent surgical resection for AMMs between 2004 and 2015. This study included 181 patients with likely TETs according to clinical features, serum levels of tumor markers and autoimmune-antibodies, and radiological findings. In addition, AMMs likely TETs were classified into resectable or unresectable tumors. We retrospectively reviewed the diagnostic process of those patients and validated surgical resection of AMMs without a definitive diagnosis. RESULTS: Among 254 patients, 181 were suspected of having a TET based on the serum levels of tumor markers and autoimmune-antibodies and the radiological findings. Of them, 157 patients were deemed resectable and underwent surgical resection without histological confirmation, and 144 (92%) were diagnosed with TETs in the final pathological examinations. In 13 patients with non-TETs, the tumors were difficult to differentiate from TETs by imaging and clinical findings alone. CONCLUSIONS: A total of 92% of patients suspected of having a TET and who underwent complete resection without pathological confirmation were accurately diagnosed and properly treated. Surgical resection without a definitive diagnosis was feasible in patients suspected of having a TET when they were considered resectable.

[Delayed Tracheal Perforation after Pulmonary Resection for Lung Cancer].

We have experienced a case of delayed tracheal perforation after pulmonary resection using soft coagulation system. A 58-year-old male underwent operation for primary lung cancer. A soft coagulation system was used for oozing near upper mediastinal lymph nodes. The patient was discharged on postoperative day 8 in a good condition, however sudden tracheal perforation and was occurred on postoperative day 30. An emergency operation revealed that improper use of the soft coagulation system might cause a necrosis of the bronchial wall. Although, a soft coagulation system is useful to control bleeding from small vessels such as bronchial arteries and lymph nodes, this system is different from conventional electrocautery and requires some attention when using.

Wogonin attenuates ovalbumin antigen-induced neutrophilic airway inflammation by inhibiting th17 differentiation.

Allergic airway inflammation is generally considered to be a Th2-type immune response. Recent studies, however, have demonstrated that Th17-type immune responses also play important roles in this process, particularly in the pathogenesis of neutrophilic airway inflammation, a hallmark of severe asthma. We scrutinized several Kampo extracts that reportedly exhibit anti-inflammatory activity by using in vitro differentiation system of human and mouse naïve T cells. We found that hange-shashin-to (HST) and oren-gedoku-to (OGT) possess inhibitory activity for Th17 responses in vitro. Indeed, wogonin and berberine, major components common to HST and OGT, exhibit Th17-inhibitory activities in both murine and human systems in vitro. We therefore evaluated whether wogonin suppresses OVA-induced neutrophilic airway inflammation in OVA TCR-transgenic DO11.10 mice. Consequently, oral administration of wogonin significantly improved OVA-induced neutrophilic airway inflammation. Wogonin suppressed the differentiation of naïve T cells to Th17 cells, while showing no effects on activated Th17 cells.

Coenzyme A contained in mothers' milk is associated with the potential to induce atopic dermatitis.

T(h)2 adjuvant activity can be qualitatively and quantitatively evaluated using a mixed lymphocyte reaction and by changes in the intracellular cyclic adenosine 3',5'-monophosphate concentration, using human dendritic cells in vitro. The current study shows that mothers, whose children (n = 55) developed atopic dermatitis (AD) within 6 months after birth, often demonstrate a higher T(h)2 adjuvant activity in their milk, in comparison to those whose children did not develop such symptoms. Such an activity was recovered in a liquid phase of mothers' milk and was eluted as a single fraction by reversed-phase HPLC. Further analysis of this fraction by mass spectrometry showed that signals originating from a factor with a molecular weight of 767.53 are observed, exclusively in milk with a high T(h)2 adjuvant activity. The mass is exactly that of Coenzyme A (CoA), and indeed, a low concentration of CoA exhibited T(h)2 adjuvant activity both in vitro and in vivo. Moreover, mesenteric lymph node non-T cells obtained from mice that were orally treated with CoA led allogeneic naive CD4(+) T cells to differentiate into T(h)2. Furthermore, the oral administration of CoA induced rough skin, hyperplasia of the epidermis, hypergranulosis in the spinous layer and the thickening of the stratum in mice. These data collectively indicate that some of the patients with AD were exposed to mothers' milk carrying high T(h)2 adjuvant activity right after birth, which may be attributable to presence of CoA contained in the milk.

Qualitative evaluation of adjuvant activities and its application to Th2/17 diseases.

Dendritic cells (DCs) are antigen-presenting cells specialized to activate naive T lymphocytes and initiate primary immune responses. The different classes of specific immune responses are driven by the biased development of antigen-specific helper T cell subsets - that is, Th1, Th2, and Th17 cells - that activate different components of cellular and humoral immunity. DCs reside in an immature state in many nonlymphoid tissues such as the skin or airway mucosa which are highly exposed to allergens, pathogens, and chemicals. T cell receptor stimulation with costimulation allows naive Th cells to develop into effector cells, normally accompanied by high-level expression of selective sets of cytokines. The balance of these cytokines and the resulting class of immune responses depend on the conditions under which DCs are primed. Immunomodulators such as lipopolysaccharides/forskolin/curdlan change the nature of DCs to induce Th1/Th2/Th17 cells thereby designated Th1/Th2/Th17 adjuvants. We have recently found that such activities can be scrutinized by using mixed lymphocyte reaction, cAMP, and differential expression of Notch ligand isoforms. Application of these methods for the analyses of atopic dermatitis and experimental autoimmune encephalomyelitis will be discussed.

Dopamine D1-like receptor antagonist attenuates Th17-mediated immune response and ovalbumin antigen-induced neutrophilic airway inflammation.

Allergic airway inflammation is generally considered a Th2-type immune response. Recent studies, however, demonstrated that Th17-type immune responses also play important roles in this process, especially in the pathogenesis of neutrophilic airway inflammation, a hallmark of severe asthma. We previously reported that dendritic cells release dopamine to naive CD4(+) T cells in Ag-specific cell-cell interaction, in turn inducing Th17 differentiation through dopamine D1-like receptor (D1-like-R). D1-like-R antagonist attenuates Th17-mediated diseases such as experimental autoimmune encephalomyelitis and autoimmune diabetes. However, the effect of antagonizing D1-like-R on Th17-mediated airway inflammation has yet to be studied. In this study, we examined whether D1-like-R antagonist suppresses OVA-induced neutrophilic airway inflammation in OVA TCR-transgenic DO11.10 mice and then elucidated the mechanism of action. DO11.10 mice were nebulized with OVA or PBS, and some mice received D1-like-R antagonist orally before OVA nebulization. D1-like-R antagonist significantly suppressed OVA-induced neutrophilic airway inflammation in DO11.10 mice. It also inhibited the production of IL-17 and infiltration of Th17 cells in the lung. Further, D1-like-R antagonist suppressed the production of IL-23 by lung CD11c(+) APCs. In contrast, D1-like-R antagonist did not increase Foxp3(+) regulatory T cells in the lung. D1-like-R antagonist neither suppressed nonspecific LPS-induced neutrophilic airway inflammation nor OVA-induced eosinophilic airway inflammation. These results indicate that D1-like-R antagonist could suppress Th17-mediated neutrophilic airway inflammation, raising the possibility that antagonizing D1-like-R serves as a promising new strategy for treating neutrophil-dominant severe asthma.

Curdlan induces DC-mediated Th17 polarization via Jagged1 activation in human dendritic cells.

BACKGROUND: Th17-inducing activity is carried by certain polysaccharides such as beta-glucan derived from Candia albicans. Our previous studies have shown that Th1- and Th2-inducing activities can be qualitatively evaluated by the expression patterns of Notch ligand isoforms, using human monocyte-derived dendritic cells (Mo-DCs) and some leukemic cell lines such as THP-1. The association of Th17-inducing activities with Notch ligand expression patterns has been unclear. METHODS: Mo-DCs from healthy volunteers were co-cultured with HLA-DR-nonshared allogeneic CD4+ naïve T cells to induce a mixed lymphocyte reaction, in the presence of adjuvants, such as curdlan. Culture supernatants were assayed for IFNgamma, IL-5 and IL-17 by an enzyme-linked immunosorbent assay (ELISA). Notch ligand expression on Mo-DCs and THP-1 cells was evaluated by using RT-PCR. RESULTS: The present study shows that curdlan, one of the beta-glucans, has the ability to induce DC-mediated Th17 differentiation. It is also interesting to note that Jagged1 mRNA in Mo-DCs and THP-1 cells is up-regulated by curdlan. Furthermore, polyclonal anti-Jagged1 antibody inhibited such DC-mediated Th17 differentiation. CONCLUSIONS: This study suggests that curdlan induces human DC-mediated Th17 polarization via Jagged1 activation in DCs.

D1-like receptor antagonist inhibits IL-17 expression and attenuates crescent formation in nephrotoxic serum nephritis.

BACKGROUND/AIMS: A dopamine type 1-like receptor (D1-like-R) expressed on dendritic cells was involved in Th17 cell differentiation of naive CD4(+) T cells. Thus, we treated mice with nephrotoxic serum nephritis (NTN) with a D1-like-R antagonist to test whether Th17 cells play a role in this kidney disease. METHODS: The SCH group of nephritic mice was administered with a D1-like-R antagonist, SCH23390, from day 0 to day 13. The kidney and spleen were collected at sacrifice on day 14. Glomerular pathology and CCR6(+) cell infiltration were quantitatively evaluated. IL-4, IFN-gamma and IL-17 mRNA levels in the kidney, and IFN-gamma and IL-17 concentrations in the supernatants from splenocytes activated in vitro were measured. RESULTS: Crescent formation had significantly developed in the positive control (PC) group of untreated, nephritic mice, which was suppressed in the SCH group. Glomerular infiltration of CCR6(+) cells was also noted in the PC group, which was abolished in the SCH group. Renal IL-17 and IFN-gamma mRNA levels were significantly reduced in the SCH group compared with the PC group. Additionally, in vitro activation augmented IFN-gamma induction, but suppressed IL-17 induction by splenocytes from the SCH group compared with those from the PC group. CONCLUSION: We identified treatment with a D1-like-R antagonist inhibited IL-17 expression and attenuated crescent formation in NTN mice.

Dopamine D1-like receptor antagonist, SCH23390, exhibits a preventive effect on diabetes mellitus that occurs naturally in NOD mice.

Dopamine receptors have five isoforms, termed D1-D5. The D1 and D5 receptors form the D1-like group that couples with the Galphas class of G proteins, while D2, D3 and D4 form the D2-like group that couples with the Galphai class of G proteins. In our previous studies, a D1-like-R antagonist, SCH23390, inhibited DC-mediated Th17 differentiation and exhibited preventive and therapeutic effects on experimental autoimmune encephalomyelitis (EAE) in mice. We herein demonstrate in the current study that in the pancreas obtained from NOD mice, islet infiltrates appear to be composed of mononuclear cells positive for IL-23R, one of the specific markers for Th17. Thereafter, NOD mice were orally administered SCH23390 from week 6 to week 26. At week 26, 67% and 25% of mice developed diabetes in the control and the SCH23390 groups, respectively (p<0.05). A histological examination of SCH23390-treated mice exhibited a typical normal islet structure with no signs of periductal and perivascular infiltrates, whereas the islets from vehicle controls showed insulitis. In week 26, spleen cells were re-stimulated with anti-CD3 and anti-CD28 antibodies in vitro and exhibited an augmentation of IFNgamma induction and the suppression of IL-17 induction in the SCH23390-treated mice. These findings indicate that antagonizing D1-like-R suppresses IL-17 expression, thereby leading to a decreased occurrence of NOD.

Dopamine released by dendritic cells polarizes Th2 differentiation.

A major neurotransmitter dopamine transmits signals via five different seven transmembrane G protein-coupled receptors termed D1-D5. It is now evident that dopamine is released from leukocytes and acts as autocrine or paracrine immune modulator. However, the role of dopamine for dendritic cells (DCs) and T(h) differentiation remains unclear. We herein demonstrate that human monocyte-derived dendritic cells (Mo-DCs) stored dopamine in the secretary vesicles. The storage of dopamine in Mo-DCs was enhanced by forskolin and dopamine D2-like receptor antagonists via increasing cyclic adenosine 3',5'-monophosphate (cAMP) formation. Antigen-specific interaction with naive CD4(+) T cells induced releasing dopamine-including vesicles from Mo-DCs. In naive CD4(+) T cells, dopamine dose dependently increased cAMP levels via D1-like receptors and shifts T-cell differentiation to T(h)2, in response to anti-CD3 plus anti-CD28 mAb. Furthermore, we demonstrated that dopamine D2-like receptor antagonists, such as sulpiride and nemonapride, induced a significant DC-mediated T(h)2 differentiation, using mixed lymphocyte reaction between human Mo-DCs and allogeneic naive CD4(+) T cells. When dopamine release from Mo-DCs is inhibited by colchicines (a microtubule depolymerizer), T-cell differentiation shifts toward T(h)1. These findings identify DCs as a new source of dopamine, which functions as a T(h)2-polarizing factor in DC-naive T-cell interface.

B cell chemoattractant CXCL13 is preferentially expressed by human Th17 cell clones.

Th 17 cells represent a novel subset of CD4+ T cells that have a protective effect against extracellular microbes, while they are also responsible for autoimmune disorders in mice. However, the protein expression profile of Th17 cells remains to be clarified. In this study, we report an effective method to establish human allo-reactive Th17 cell clones and demonstrate that human Th17, but not Th1 or Th2, cells express B cell chemoattractant CXCL13, by using DNA chips, RT-PCR, and ELISA. Such a pattern was also the case in Candida albicans-specific Th17 clones and synovial fluid specimens obtained from patients with rheumatoid arthritis. The biological implication of this finding is discussed.

Antagonizing dopamine D1-like receptor inhibits Th17 cell differentiation: preventive and therapeutic effects on experimental autoimmune encephalomyelitis.

Five types of dopamine receptors, termed D1 to D5, have been identified to date. The D1 and D5 receptors form the D1-like group that couples with the Galphas class of G proteins, while D2, D3 and D4 form the D2-like group that couples with the Galphai class of G proteins. A D2-like-receptor (D2-like-R) antagonist L750667 induced dendritic cell (DC)-mediated Th17 differentiation. In contrast, a D1-like-R antagonist SCH23390 inhibited DC-mediated Th17 differentiation. The D1-like-Rs were expressed on both DCs and T cells, whereas D2-like-Rs were marginally expressed on CD4+CD45RA+ naïve T cells. In addition, SCH23390 had the ability to prevent experimental autoimmune encephalomyelitis (EAE) in mice. Spleen cells from EAE mice showed decreased IL-17 production, when SCH23390 was administered. Adoptive transfer of DCs treated with SCH23390 successfully prevented EAE. These findings indicate that antagonizing D1-like-Rs on DCs inhibits Th17 differentiation, thereby leading to an amelioration of EAE.