Pleurotus ferulae water extract enhances the maturation and function of murine bone marrow-derived dendritic cells through TLR4 signaling pathway

Dendritic cells (DCs) play important roles in the regulation of immune system, which link innate and adaptive immune responses. Mature DCs produced interleukin (IL)-12 promote optimal type 1 T helper (Th1) cells and cytotoxic T lymphocytes. The extracts of traditional herbal medicines have been shown to enhance immune responses through promoting the maturation and cytokine production of DCs. Here, we investigated the effects of Pleurotus ferulae water extract (PFWE) on the maturation and function of bone marrow–derived DCs (BM–DCs). Upon PFWE treatment, BM–DCs dose-dependently upregulated the expression of CD40, CD80, CD86 and MHC II and increased the production of IL-12, IL-6 and tumor necrosis factor (TNF)-α but not for IL-10, which is mediated by TLR4 signaling pathway, at least partially. The production of prostaglandin E2 (PGE2) in BM–DCs was decreased by the treatment of PFWE. Moreover, PFWE treatment decreased the expression of active caspase-3 but increased the expression of CCR7. PFWE treated DCs enhanced the proliferation of allogenic CD8⁺ T cells and the capacity of antigen presenting to autologous CD8⁺ T cells. The combination of PFWE and CpG–ODN further enhanced the maturation and function of murine BM–DCs. The results showed that PFWE could enhance the maturation and function of DCs through TLR4 signaling pathway and has additive effect when combined with CpG–ODN, suggesting that PFWE alone or combined with CpG–ODN could be used to enhance the immune responses.     

Infection of mouse bone marrow-derived dendritic cells by live attenuated Japanese encephalitis virus induces cells maturation and triggers T cells activation

An attenuated Japanese encephalitis virus (JEV) strain SA14-14-2, generated from the wild strain SA14, is an effective live vaccine against JEV infection. It has led to a significant decrease in JEV infection around the world. Although it is highly effective, the mechanism for its robust immunity was not well investigated. In this study, the interaction of SA14-14-2 with bone marrow-derived dendritic cells (bmDCs) was investigated. Our results showed that the infection of bmDCs with SA14-14-2 resulted in viral replication and upregulation of bmDC maturation marker molecules (CD40, CD80, CD83 and MHC I). SA14-14-2 infection also stimulated the production of interferon-α (IFN-α), monocyte chemoattractant protein-1 (MCP-1/CCL2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) of bmDC. Both MLR and ELISPOT assay showed an enhanced allostimulatory capacity of SA14-14-2-infected bmDCs. Furthermore, the SA14-14-2-infected bmDCs impaired the expansion of Foxp3+ regulatory T (Treg) cells with immunosuppressive potential, suggesting that SA14-14-2 infection induced antiviral immunity rather than immunosuppression. Taken together, our results indicated that SA14-14-2 infection caused bmDC maturation, changed the expression profiles of several cytokines, and triggered T cell activation. This offered an insight in the immunologic mechanisms associated with the high efficiency of the SA14-14-2 vaccine.     

Dietary supplementation with white button mushroom enhances natural killer cell activity in C57BL/6 mice

Mushrooms are reported to possess antitumor, antiviral, and antibacterial properties. These effects of mushrooms are suggested to be due to their ability to modulate immune cell functions. However, a majority of these studies evaluated the effect of administering extracts of exotic mushrooms through parental routes, whereas little is known about the immunological effect of a dietary intake of white button mushrooms, which represent 90% of mushrooms consumed in the U.S. In this study, we fed C57BL/6 mice a diet containing 0, 2, or 10% (wt/wt) white button mushroom powder for 10 wk and examined indices of innate and cell-mediated immunity. Mushroom supplementation enhanced natural killer (NK) cell activity, and IFNgamma and tumor necrosis factor-alpha (TNFalpha) production, but only tended to increase IL-2 (P = 0.09) and did not affect IL-10 production by splenocytes. There were significant correlations between NK activity and production of IFNgamma (r = 0.615, P < 0.001) and TNFalpha (r = 0.423, P = 0.032) in splenocytes. Mushroom supplementation did not affect macrophage production of IL-6, TNFalpha, prostaglandin E(2), nitric oxide, and H(2)O(2), nor did it alter the percentage of total T cells, helper T cells (CD4(+)), cytotoxic or suppressive T cells (CD8(+)), regulatory T cells (CD4(+)/CD25(+)), total B cells, macrophages, and NK cells in spleens. These results suggest that increased intake of white button mushrooms may promote innate immunity against tumors and viruses through the enhancement of a key component, NK activity. This effect might be mediated through increased IFNgamma and TNFalpha production.     

Interactions of proteoliposomes from serogroup B Neisseria meningitidis with bone marrow-derived dendritic cells and macrophages: adjuvant effects and antigen delivery

Exposure to proteoliposomes from serogroup B Neisseria meningitidis (PL) induced up-regulation of MHC-II, MHC-I, CD40, CD80 and CD86 expression on the surface of murine bone marrow-derived dendritic cells (DC). CD40, CD80 and CD86 were up-regulated on bone marrow-derived macrophages (MPhi) upon stimulation with PL. Both DC and MPhi released TNFalpha, but only DC produced IL12(p70) in response to PL. A small increase in the expression of MHC-II, CD40 and CD86, as well as production of IL12(p70), was observed on the cell surface of DC, but not MPhi from LPS-non-responder C3H/HeJ after exposure to PL. DC, but not MPhi, incubated with PL containing ovalbumin (PL-OVA) presented OVA-specific peptides to CD4+ and CD8+ OVA-specific T-cell hybridomas. These data clearly indicate that PL exert an immunomodulatory effect on DC and MPhi, with some contribution of non-LPS components besides the main role of LPS. The work also shows the potential of PL as a general system to deliver antigens to DC for presentation to CD4+ and CD8+ T-cells.     

树突状细胞和巨噬细胞提呈日本血吸虫抗原作用

目的　探讨树突状细胞和巨噬细胞提呈日本血吸虫抗原的作用。方法　利用日本血吸虫可溶性虫卵抗原 (SEA)致敏树突状细胞和巨噬细胞 ,将致敏的细胞免疫小鼠 3次 ,检测血清抗体水平。结果　抗原致敏树突状细胞免疫组小鼠血清平均抗体水平 ( 0 10 6 8± 0 0 16 )高于抗原致敏巨噬细胞免疫组小鼠 ( 0 0 880± 0 0 17) ,且高于未处理树突状细胞免疫组小鼠 ( 0 0 82 5± 0 0 12 )。结论　树突状细胞提呈日本血吸虫抗原的作用强于巨噬细胞 ,是日本血吸虫感染中的主要抗原提呈细胞     

Induction of cytotoxic T lymphocyte responses by cholera toxin-treated bone marrow-derived dendritic cells

Cholera toxin (CT), a powerful mucosal adjuvant, is a potent inducer of Th2-type responses via activation of co-stimulatory molecules for the induction of IgA antibody responses. Less appreciated is the ability of CT to induce and regulate cytotoxic T lymphocyte (CTL) responses. In order to help for clarifying mechanisms underlying the CTL-inducing ability of CT, we have examined the effects of CT on dendritic cells (DCs) that could lead to the induction of cytotoxic CD8(+) T cells. When bone marrow-derived DCs (BM-DCs) were cultured with CT in vitro, B7-1 but not B7-2 molecules were significantly enhanced and allogenic CTL responses were induced. Also, increased numbers of IFN-gamma-secreting CD8(+) T cells were elicited when CT-treated BM-DCs were co-cultured with allogenic CD8(+) CTLs. Antibody blockade of B7-1 on CT-treated BM-DCs suppressed allogenic CTL responses, further indicating the importance of CT-induced B7-1 molecules on DCs for the acquisition of cytolytic function by CTL precursors. CD40 signaling was proven not necessary for the CT-induced CTL response since CT-treated CD40(-/-) BM-DCs developed CTL responses equivalent to those detected in CT-treated BM-DCs derived from normal mice. Our results suggest that CT-treated DCs are effective inducers of CD8(+) CTL, and this induction is mediated through CT's ability to enhance B7-1 expression on DCs.     

Effect of mite antigens on antigen presenting cells/macrophages in mice

The effect of mite antigens on murine lymphocytes and macrophages was studied in vitro. Antigens prepared from Dermatophagoides farinae bodies (Dfb) or recombinant Mag3, glutathione-S transferase (GST)-fused mite antigen, stimulated murine spleen cells to proliferate. The responder cells were B cells, because the response was sensitive to anti-Ig antibody and C treatment, but not to anti-Thy 1 antibody and C treatment. The response was not due to lipopolysaccharide contamination, a representative B-cell mitogen, because polymyxin B column-passed Dfb significantly stimulated B cells, and GST protein alone did not stimulate them. Alloantigen presenting activity was increased in mite antigen-treated B cells and spleen adherent cells. Mite antigens stimulated CD80 and the major histocompatibility complex (MHC) class II molecule expression, but suppressed CD86 expression on B cells and spleen adherent cells that were detected by a flow cytofluorometer. Antibodies to the MHC class II molecules, CD80 and CD86 blocked the alloantigen-presenting activity. Furthermore, mite antigens stimulated B cells and spleen adherent cells to produce cytokines. These results suggest that mite antigens have a stimulating activity on antigen-presenting cells/macrophages and modulate immune responses.     

碘对小鼠骨髓树突状细胞前体表型及功能影响

目的 探讨碘对小鼠树突状细胞(dendritic cell,DC)前体表型及功能的影响.方法 选雌性C57BL/6 J小鼠40只,按碘摄入量随机分为适碘组(NI)、低碘组(LI)、10倍碘过量组(10H I)、50倍碘过量组(50H I)4组,喂养8个月后检测小鼠DC表面分子表达和培养上清中白细胞介素-12(interleukin-12,IL-12)水平以及DC刺激T细胞的增殖能力.结果 LI组小鼠DC表面分子CD40⁺CD11 c⁺、CD80⁺CD11 c⁺、CD86⁺CD11 c⁺、MHC-Ⅱ⁺CD11 c⁺在CD11 c⁺细胞中所占比例均低于NI组小鼠,差异均有统计学意义(P<0.05);50H I组小鼠DC表面分子CD40⁺CD11 c⁺、CD80⁺CD11 c⁺、CD86⁺CD11 c⁺、MHC-Ⅱ⁺CD11 c⁺在CD11 c⁺细胞中所占比例均高于NI组小鼠,差异均有统计学意义(P<0.05);LI组小鼠DC培养上清中细胞因子IL-12浓度为(275.8±32.6)pg/mL,低于NI组小鼠的(548.7±51.3)pg/mL(P<0.01);50H I组小鼠DC培养上清中细胞因子IL-12浓度为(963.2±83.4)pg/mL,高于NI组小鼠(P<0.01);LI组的刺激指数(SI)为(5.23±1.96),低于NI组小鼠的(8.61±2.15)(P<0.05);50H I组小鼠的SI为(12.38±2.61),高于NI组小鼠(P<0.05).结论 摄入一定水平的碘可诱导小鼠DC前体的增殖和成熟,提高机体的免疫功能.     

White button mushroom (Agaricus bisporus) lowers blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats

Agaricus bisporus (white button mushroom; WBM) contains high levels of dietary fibers and antioxidants including vitamin C, D, and B₁₂; folates; and polyphenols that may provide beneficial effects on cardiovascular and diabetic diseases. The objective of this study was to examine the hypothesis that intake of the fruiting bodies of WBM regulates anticholesterolemic and antiglycemic responses in rats fed a hypercholesterolemic diet (0.5% cholesterol; 14% fat) and rats with type 2 diabetes induced by injection of streptozotocin (STZ) (50 mg/kg body weight), respectively. The STZ-induced diabetic male Sprague-Dawley rats fed the Agaricus bisporus powder (ABP; 200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose and triglyceride (TG) concentrations (24.7% and 39.1%, respectively), liver enzyme activities, alanine aminotransferase and aspartate aminotransferase (11.7% and 15.7%, respectively), and liver weight gain (P < .05). In hypercholesterolemic rats, oral feeding of ABP for 4 weeks resulted in a significant decrease in plasma total cholesterol (TC) and low-density lipoprotein (LDL) (22.8% and 33.1%, respectively) (P < .05). A similar significant decrease in hepatic cholesterol and TG concentrations was observed (36.2% and 20.8%, respectively) (P < .05). Decrease in TC, LDL, and TG concentrations was accompanied by a significant increase in plasma high-density lipoprotein concentrations. It was concluded that A bisporus mushroom had both hypoglycemic and hypolipidemic activity in rats.     

Human natural killer cell function and their interactions with dendritic cells

Natural killer (NK) cells have long been considered as "primitive" and "non-specific" effector cells. However, the past 10 years have witnessed dramatic progress in our understanding of how NK cells function and their role in innate defenses. Thanks to specialized inhibitory receptors specific for MHC-class I molecules, they can sense the decrease or loss of these molecules, a typical condition of potentially dangerous cells such as tumor or virally-infected cells. NK cell triggering and lysis of these cells is mediated by several activating receptors and co-receptors that have recently been identified and cloned. While normal cells are usually resistant to the NK-mediated attack, a remarkable exception is represented by dendritic cells (DC). In their immature form (iDC), they are susceptible to NK-mediated lysis because of the expression of low levels of surface MHC-class I molecules. Since the process of DC maturation (mDC) is characterized by the surface expression of high levels of MHC-class I molecules, mDC become resistant to NK cells. Exposure to live bacteria induces rapid DC maturation and, thus, resistance to NK cells. The cross-talk between DC and NK cells is more complex and involves also a DC-dependent NK cell activation and proliferation. Thus, two important players of the innate immunity may be involved in a coordinated regulation of critical events occurring at the interface between innate and adaptive immunity.     

Evaluation of murine bone marrow-derived dendritic cells loaded with inactivated virus as a vaccine against Japanese encephalitis virus

Japanese encephalitis (JE) is a serious infectious disease in southern and eastern Asia. Design and development of safer and more efficacious vaccines against Japanese encephalitis virus (JEV) is a high-priority target in the world. Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) playing a central and unique role in the generation of primary T-cell responses, and are considered attractive “live adjuvants” for vaccination and immunotherapy against cancer and infectious diseases. In this study, mouse bone marrow-derived dendritic cells (bmDCs were generated and stimulated with inactivated JEV in vitro. BALB/c mice were immunized with stimulated bmDCs and then challenged with JEV wild-type strain. The neutralization antibody, interferon gamma (IFN-γ), tumor necrosis factors alpha (TNF-α) or interleukin-6 (IL-6), and virus-specific CD8+ cytotoxic T-lymphocyte (CTL) levels, as well as survival rates, were analyzed and compared with inactivated vaccine and DCs control groups. The results demonstrated that intravenous (i.v.) injection of 2 × 10⁵ JEV-pulsed bmDCs into each mouse produced notable levels of JEV-specific neutralizing antibodies and higher levels of CD8+ CTL, IFN-γ and TNF-α compared with JEV-inactivated vaccine. Furthermore, stimulated bmDCs could elicit a highly protective efficacy (90%) against JEV challenge. It suggests that stimulated bmDCs can be considered as an attractive “live adjuvant” for vaccination against JEV infection.     

大鼠骨髓来源树突状细胞的体外诱导扩增及其功能鉴定

目的探讨体外诱导和扩增大鼠骨髓来源树突状细胞（DC）的方法，并观察其表型及功能特性。方法取得大鼠骨髓细胞后，去除红细胞，加入重组大鼠粒细胞／巨噬细胞集落刺激因子（rrGM-CSF）、重组大鼠白细胞介素4（rrIL-4）培养2周；在光镜和扫描电镜下观察培养DC的形态学特征，流式细胞仪检测DC表面MHC-Ⅱ、CD80、CD86的表达水平，混合淋巴细胞反应检测其刺激同种T细胞增殖能力。结果细胞培养8d后，经倒置显微镜和电镜观察DC出现典型形态，培养6d的DC具有不成熟表型，流式细胞仪检测MHC-Ⅱ为（29．03±4．39）％、CD80为（21．98±7．08）％，CD86为（25．94±6．80）％，刺激同种T细胞增殖能力极低，而培养12dDC的MHC-Ⅱ为（74．05±5．97）％、CD80为（79．85±6．53）％，CD86为（81．00±7．47）％，刺激同种T细胞增殖能力明显增强。结论大鼠骨髓来源干细胞可经联合应用细胞因子诱导培养为具有典型形态特征及功能的DC，为进一步研究其在移植免疫学中的应用奠定基础。     

Infection of mouse bone marrow-derived dendritic cells with recombinant adenovirus vectors leads to presentation of encoded antigen by both MHC class I and class II molecules-potential benefits in vaccine design

Dendritic cells (DCs) are highly specialised antigen-presenting cells (APCs) that are essential for the initiation and modulation of T cell-mediated immune responses. In order to induce effective CTL responses against most infections and tumours, DCs must prime both CD4(+) and CD8(+) antigen-specific T cells. It is, therefore, important in vaccine design to produce antigen-delivery systems that lead to the simultaneous presentation of multiple histocompatibility complex (MHC) class I- and class II-restricted antigenic peptides by DCs. In this study, the infection of immature mouse bone marrow-derived DCs (BMDCs) with recombinant adenovirus (rAd) vectors led to a marked upregulation of surface costimulatory molecules, IL-12 p40 production and capacity to stimulate both allogeneic and antigen-specific T cells. Furthermore, infection of immature and mature BMDCs with a rAd encoding chicken ovalbumin (OVA) led to presentation of the antigen to TCR-transgenic OVA-specific CD4(+) and CD8(+) T cells. In addition, the activation state of responding CD8(+) T cells was further amplified if they recognised antigen on rAd-transduced BMDCs in the presence of antigen-specific CD4(+) T cells. The results suggest that rAd-encoded OVA protein is secreted by BMDCs, taken up by endocytosis and presented in association with MHC class II molecules for activation of OVA-specific CD4(+) T cells. Consequently, rAd-transduced immature BMDCs become better stimulators of antigen-specific CD4(+) T cells than rAd-infected mature BMDCs. Taken together, these data have important implications for vaccine design, and suggest that infection of immature DCs with rAd encoding MHC class I and class II-restricted T cell epitopes could be an efficient means of inducing effective immune responses.     

White button and shiitake mushrooms reduce the incidence and severity of collagen-induced arthritis in dilute brown non-agouti mice

Exotic mushrooms have been used in ancient Chinese medicine due to their immunomodulatory properties for the treatment and/or prevention of chronic diseases. However, only limited data exist on the health benefits of white button mushrooms (WBM), the most common in the American diet. In the current study, we investigated the effects of WBM and shiitake mushrooms (SM) on collagen-induced arthritis (CIA) using a 2 x 3 factorial design in 8-wk-old female dilute brown non-agouti mice that were fed a control diet (n = 37) or the same diet supplemented with 5% lyophilized WBM or SM (n = 27) for 6 wk. CIA was induced by immunizing mice with 100 μg bovine collagen followed by 50 μg LPS on d 20 post-collagen injection. CIA was assessed by mononuclear cell infiltration, bone erosion, plasma IL-6, TNFα, and intercellular adhesion molecule-1 (sICAM-1) concentrations. Compared with the control diet, WBM and SM tended to reduce the CIA index from 5.11 ± 0.82 to 3.15 ± 0.95 (P = 0.06) (median, 6-9 to 1-2) 31 d post-collagen injection. Whereas 58% of control mice had a CIA index ≥ 7, only 23% of WBM and 29% of SM mice did (P = 0.1). Although both types of mushrooms reduced plasma TNFα (34%, WBM; 64%, SM), only SM increased plasma IL-6 by 1.3-fold (P < 0.05). The CIA index was positively correlated with sICAM1 (r = 0.55; P < 0.05) but negatively correlated with TNFα (r = 0.34; P < 0.05). Whether mushrooms are beneficial for arthritis management remains to be investigated. To our knowledge, this is the first report demonstrating a possible health benefit of WBM in arthritis treatment.     

Vitamin D3-mediated alterations to myeloid dendritic cell trafficking in vivo expand the scope of their antigen presenting properties

The mucosal immune system provides the host with a first line of adaptive immune defense against invasion by many species of pathogenic microorganisms and their secreted products. Calcitriol, the active form of Vitamin D3 (VD3), promotes the induction of mucosal immunity in mice when added to subcutaneously administered vaccine formulations. Dendritic cells (DCs) activated at vaccination sites where VD3 is present gain the capacity to bypass sequestration in the draining lymph node and traffic to the Peyer's Patches (PP) of immunized animals. By employing protocols that allow the effective tracking of endogenous or adoptively transferred myeloid DCs in vivo, we found that VD3 influences on the trafficking of fully differentiated immature DCs were temporary, and occur without negative effects to antigen processing or peptide presentation to CD4+ T cells. In contrast, DCs differentiated from hematopoietic precursors in the presence of VD3 (conditioned DCs), were markedly compromised in their antigen presenting properties, while manifesting clear alterations to their trafficking properties in vivo. Similar to the recent finding of VD3-mediated enhancement of innate immune protection, our findings suggest that VD3 could also play an important role in controlling the types of immune effector responses elicited subsequent to either infection or vaccination.     

香菇膳食纤维复合食品改善小鼠肠道功能作用

目的 探讨香菇膳食纤维复合食品对小鼠肠道功能的改善作用。方法 随机将昆明种小鼠分为对照组、模型组、清畅胶囊组(150 mg/kg)、复合食品组(100 mg/kg),对照组与模型组蒸馏水灌胃,清畅胶囊组与复合食品组分别给予清畅胶囊与香菇膳食纤维复合食品,连续15 d;分别观察小鼠体重、肠道菌群、小肠运动、小鼠排便的变化。结果 与对照组比较,清畅胶囊组、复合食品组小鼠肠道内双歧杆菌与乳杆菌数量[分别为(9.82±0.76)、(9.67±0.71)与(9.10±0.37)、(9.02±0.19)log cfu/g]明显增加(P<0.05);与模型组比较,复合食品组小鼠小肠推进率[(49.53±12.73)%]明显升高,差异有统计学意义(P<0.05);与对照组比较,模型组小鼠首次排便时间[(141.70±14.86)min]延长、5 h排便重量[(0.22±0.06)g]下降(P<0.01);与模型组比较,清畅胶囊组、复合食品组小鼠首次排便时间[(101.40±7.56)、(92.50±10.96)min]明显缩短,5 h排便重量[(0.50±0.12)、(0.46±0.12)g]明显增加(P<0.01)。结论 香菇膳食纤维复合食品可增加小鼠肠道双歧杆菌、乳杆菌数量,具有促进肠道蠕动,改善便秘的作用。     

White button,portabella, and shiitake mushroom supplementation up-regulates interleukin-23 secretion in acute dextran sodium sulfate colitis C57BL/6 mice and murine macrophage J.744.1 cell line

Interleukin-23 (IL-23), a cytokine produced primarily by dendritic cells, is involved in host defense against gut pathogens and promotes innate immunity and inflammatory responses through the IL-23/interleukin-17 axis. We previously reported that extracts from edible mushrooms enhanced antimicrobial α-defensin production n HL60 cells. Because IL-23 is involved in defensin production, we hypothesized that edible mushrooms may modulate its secretion and gut inflammation. Eight-week-old C57BL/6 mice were fed the AIN76 diet or the same diet supplemented with 5% white button (WBM), portabella, or shiitake mushrooms. To assess in vivo and in vitro cytokine secretion, 7 to 8 mice per group received 3% dextran sodium sulfate (DSS) in drinking water during the last 5 days of the 6-week feeding period. To delineate the mechanisms by which mushrooms alter IL-23 secretion, J.744.1 cells were incubated with (100 μg/mL) WBM, portabella, and shiitake extracts without and with 100 μg/mL curdlan (a dectin-1 agonist) or 1 mg/mL laminarin (a dectin-1 antagonist). The dectin-1 receptor is a pattern-recognition receptor found in phagocytes, and its activation promotes antimicrobial innate immunity and inflammatory responses. In DSS-untreated mice, mushrooms significantly increased IL-23 plasma levels but decreased those of interleukin-6 (IL-6) (P < .05). In DSS-treated mice, mushroom-supplemented diets increased IL-6 and IL-23 levels (P < .05). Mushroom extracts potentiated curdlan-induced IL-23 secretion, and mushroom-induced IL-23 secretion was not blocked by laminarin in vitro, suggesting the involvement of both dectin-1–dependent and dectin-1–independent pathways. Although all mushrooms tended to increase IL-6 in the colon, only WBM and shiitake tended to increase IL-23 levels. These data suggest that edible mushrooms may enhance gut immunity through IL-23.     

Repeated antigen painting and sublingual immunotherapy in mice convert sublingual dendritic cell subsets

The sublingual mucosa (SLM) is utilized as the site for sublingual immunotherapy (SLIT) to induce tolerance against allergens. The contribution of SLM-dendritic cells (SLM-DCs) has not been clarified. The aim of this study was to examine the dynamics and phenotype of SLM-DCs after topical antigen painting and SLIT. SLM-DCs were histologically evaluated after FITC painting. A novel murine Japanese cedar pollinosis (JCP) model was generated and change in SLM-DCs after SLIT was examined. The density of SLM-DCs was clearly lower compared with the buccal mucosa and dorsal surface of the tongue. Topical FITC painting on the SLM induced maximal recruitment of submucosal DCs (smDCs) at 6 h, but most smDCs had vanished at 24 h. Repeated painting on the SLM induced exhaustion and conversion of the smDC phenotype. CD206^highCD11c^low round-type cells with fewer dendrites and less lymph node migration capacity became dominant. In the murine model of JCP, SLIT efficiently inhibited clinical symptoms and allergen-mediated immunological responses. SLIT markedly reduced the number of SLM-DCs, converted to the round-type dominant phenotype and inhibited the activation of regional lymph node DCs. Topical antigen painting on the SLM induced rapid exhaustion and conversion of smDCs. The unique dynamics of SLM-DCs may contribute to tolerance induction in SLIT.