1.Mucosal dendritic cells shape mucosal immunity.
Sun Young CHANG ; Hyun Jeong KO ; Mi Na KWEON
Experimental & Molecular Medicine 2014;46(3):e84-
Dendritic cells (DCs) are key modulators that shape the immune system. In mucosal tissues, DCs act as surveillance systems to sense infection and also function as professional antigen-presenting cells that stimulate the differentiation of naive T and B cells. On the basis of their molecular expression, DCs can be divided into several subsets with unique functions. In this review, we focus on intestinal DC subsets and their function in bridging the innate signaling and adaptive immune systems to maintain the homeostasis of the intestinal immune environment. We also review the current strategies for manipulating mucosal DCs for the development of efficient mucosal vaccines to protect against infectious diseases.
Animals
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Dendritic Cells/*immunology/metabolism
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Humans
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Immunity, Mucosal
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Intestinal Mucosa/cytology/*immunology
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T-Lymphocytes, Helper-Inducer/immunology
2.New era for mucosal mast cells: their roles in inflammation, allergic immune responses and adjuvant development.
Yosuke KURASHIMA ; Hiroshi KIYONO
Experimental & Molecular Medicine 2014;46(3):e83-
To achieve immune homeostasis in such a harsh environment as the intestinal mucosa, both active and quiescent immunity operate simultaneously. Disruption of gut immune homeostasis leads to the development of intestinal immune diseases such as colitis and food allergies. Among various intestinal innate immune cells, mast cells (MCs) play critical roles in protective immunity against pathogenic microorganisms, especially at mucosal sites. This suggests the potential for a novel MC-targeting type of vaccine adjuvant. Dysregulated activation of MCs also results in inflammatory responses in mucosal compartments. The regulation of this yin and yang function of MCs remains to be elucidated. In this review, we focus on the roles of mucosal MCs in the regulation of intestinal allergic reaction, inflammation and their potential as a new target for the development of mucosal adjuvants.
Adjuvants, Immunologic/*therapeutic use
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Animals
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Humans
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Hypersensitivity/*immunology/prevention & control
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Inflammation/immunology/metabolism/prevention & control
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Intestinal Mucosa/cytology/*immunology
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Mast Cells/*immunology
3.Antigen targeting to M cells for enhancing the efficacy of mucosal vaccines.
Experimental & Molecular Medicine 2014;46(3):e85-
Vaccination is one of the most successful applications of immunology and for a long time has depended on parenteral administration protocols. However, recent studies have pointed to the promise of mucosal vaccination because of its ease, economy and efficiency in inducing an immune response not only systemically, but also in the mucosal compartment where many pathogenic infections are initiated. However, successful mucosal vaccination requires the help of an adjuvant for the efficient delivery of vaccine material into the mucosa and the breaking of the tolerogenic environment, especially in oral mucosal immunization. Given that M cells are the main gateway to take up luminal antigens and initiate antigen-specific immune responses, understanding the role and characteristics of M cells is crucial for the development of successful mucosal vaccines. Especially, particular interest has been focused on the regulation of the tolerogenic mucosal microenvironment and the introduction of the luminal antigen into the lymphoid organ by exploiting the molecules of M cells. Here, we review the characteristics of M cells and the immune regulatory factors in mucosa that can be exploited for mucosal vaccine delivery and mucosal immune regulation.
Administration, Oral
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Animals
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Antigens, Bacterial/*immunology
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Antigens, Viral/*immunology
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Bacterial Vaccines/administration & dosage/*immunology
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Humans
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Immunity, Mucosal
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Intestinal Mucosa/cytology/*immunology
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Peyer's Patches/cytology/*immunology
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Viral Vaccines/administration & dosage/*immunology
4.Mucosal mast cell-derived chondroitin sulphate levels in and worm expulsion from FcRgamma-knockout mice following oral challenge with Strongyloides venezuelensis.
Denis Nnabuike ONAH ; Yukifumi NAWA
Journal of Veterinary Science 2004;5(3):221-226
Mucosal mast cell-derived chondroitin sulphates (sulphated proteoglycans) were assayed in gut washings and homogenate of FcRgamma-knockout (KO) and wild-type (WT) C57BL/6 mice challenged with Strongyloides venezuelensis in order to assess their possible role in secondary immunity against enteric nematodes. Groups of immune KO and WT mice were challenged by oral gavage with 300 infective larvae (L3). Establishment of infection was assessed by daily faecal analysis to determine the number of eggs per gram of faeces (EPG) and by adult worm recovery on days 5 and 13 post challenge. Mucosal mast cell (MMC) counts were done on days 5 and 13 post challenge while MMC-derived chondroitin sulphates in gut washings (days 1 and 5) and homogenate (day 8) were assayed by high performance liquid chromatography (HPLC). Results showed that patent infection occurred in challenged KO but not WT mice despite significantly higher mastocytosis in jejunal sections of KO than WT mice (p<0.001). Similarly but against prediction, significantly higher concentration of MMC-derived chondroitin sulphates was observed in gut homogenate of KO than WT mice (p<0.05). In contrast, significantly higher concentration of chondroitin sulphates was observed in gut washings of WT than KO mice (p<0.05). These results suggest that MMC in KO mice failed to release sufficient amount of sulphated proteoglycans into the gut lumen as did the WT mice, which may have been part of the hostile environment that prevented the establishment in and eventual expulsion of adult S. venezuelensis from the gut of WT mice following challenge.
Animals
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Cell Count/veterinary
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Chondroitin Sulfates/*immunology/metabolism
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Chymases
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Feces/parasitology
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Intestinal Diseases, Parasitic/immunology/*veterinary
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Intestinal Mucosa/cytology/immunology/parasitology
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Jejunum/cytology/immunology/parasitology
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Male
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Mast Cells/immunology/metabolism/*parasitology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Parasite Egg Count/veterinary
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Receptors, IgG/*immunology
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Serine Endopeptidases/blood/immunology
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Specific Pathogen-Free Organisms
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Strongyloides/*immunology
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Strongyloidiasis/immunology/parasitology/*veterinary
5.T cell phenotype and intracellular IFN-gamma production in peritoneal exudate cells and gut intraepithelial lymphocytes during acute Toxoplasma gondii infection in mice.
The Korean Journal of Parasitology 2002;40(3):119-129
Although there are many reports on the splenic (systemic) T cell response after Toxoplasma gondii infection, little information is available regarding the local T cell responses of peritoneal exudate cells (PEC) and gut intraepithelial lymphocytes (IEL) following peroral infection with bradyzoites. Mice were infected with 40 cysts of the 76K strain of T. gondii, and then sacrificed at days 0, 1, 4, 7 and 10 postinfection (PI). The cellular composition and T cell responses of PEC and IEL were analyzed. The total number of PEC and IEL per mouse increased after infection, but the ratio of increase was higher in IEL. Lymphocytes were the major component of both PEC and IEL. The relative percentages of PEC macrophages and neutrophils/eosinophils increased significantly at day 1 and 4 PI, whereas those of IEL did not change significantly. The percentage of PEC NK1.1 and gamma delta T cells peaked at day 4 PI (p < 0.0001), and CD4 and CD8 alpha T cells increased continuously after infection. The percentages of IEL CD8 alpha and gamma delta T cells decreased slightly at first, and then increased. CD4 and NK1.1 T cells of IEL did not change significantly after infection. IFN-gamma-producing PEC NK1.1 T cells increased significantly from day 1 PI, but the other T cell subsets produced IFN-gamma abundantly thereafter. The proportion of IEL IFN-gamma-producing CD8 alpha and gamma delta T cells increased significantly after infection, while IEL NK1.1 T cells had similar IFN-gamma production patterns. Taken together, CD4 T cells were the major phenotype and the important IFN-gamma-producing T cell subsets in PEC after oral infection with T. gondii, whereas CD8 alpha T cells had these roles in IEL. These results suggest that PEC and IEL comprise different cell differentials and T cell responses, and according to infection route these factors may contribute to the different cellular immune responses.
Acute Disease
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Animals
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Ascitic Fluid/cytology/*metabolism
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Female
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Interferon Type II/*biosynthesis
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Intestinal Mucosa/cytology
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Lymphocytes/*metabolism
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Mice
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Mice, Inbred C57BL
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Support, Non-U.S. Gov't
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T-Lymphocyte Subsets/*immunology
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Toxoplasmosis/*immunology
6.Effects of intestinal trefoil factor combined with mucin on ability of proliferation and migration of intestinal epithelial cells after being treated by rat burn serum.
Huan WANG ; Xiu-Wen WU ; Qian-Xue WAN ; Xing JIN ; Yong SUN ; Dan WU ; Jun-Jie CAO ; Xi PENG
Chinese Journal of Burns 2011;27(5):347-352
OBJECTIVETo observe the effect of intestinal trefoil factor (ITF) combined with mucin on the ability of proliferation and migration of intestinal epithelial cells (IEC) after being treated by burn rat serum.
METHODSThe rat IEC-6 cell lines were subcultured and divided into control group (C, cultured with DMEM medium containing 10% calf serum), burn serum group (BS, cultured with DMEM medium containing 10% burn rat serum), burn serum + ITF group (B + I, cultured with DMEM medium containing 10% burn rat serum and 25 microg/mL ITF), burn serum + mucin group (B + M, cultured with DMEM medium containing 10% burn rat serum and 250 microg/mL mucin), and burn serum + ITF + mucin group (B + I + M, cultured with DMEM medium containing 10% burn rat serum, 25 microg/mL ITF, and 250 microg/mL mucin) according to the random number table. Cells were counted on post culture day (PCD) 0, 1, 2, 3, 4, reflecting cell proliferation ability. Cell migration distance was measured at post scratch hour (PSH) 12, 24, 36, 48, 72. Then, cells of each group were placed in upper compartment of Transwell chamber while the corresponding medium was respectively added into lower compartment of Transwell chamber. Cells in lower compartment of Transwell chamber were counted at post culture hour (PCH) 4, 6, 8, 10, 12, reflecting cytomorphosis ability. Data were processed with t test.
RESULTS(1) Cell proliferation ability. The cell numbers in BS group on PCD 0, 1, 2, 3, 4 were significantly less than those in C group (with t values from -16.569 to -2.613, P < 0.05 or P < 0.01). The cell number showed no statistical difference between B + I and BS groups, and between B + M and BS groups at each time point (with t values respectively from 0.037 to 0.740 and 0.116 to 0.429, P values all above 0.05). The cell number in B + I + M group on PCD 2 was respectively larger than that in BS group (t = 6.484, P < 0.01) and B + I group ( t = 3.838, P < 0.01). (2) Cell migration distance in BS group at PSH 12, 24, 36, 48, 72 was significantly shorter than that in C group (with t values from -37.594 to -6.727, P values all below 0.01). There was no obvious difference in cell migration distance between BS and B + M groups at each time point (with t values from 0.055 to 0.589, P values all above 0.05). Cell migration distance in B + I group at PSH 12, 24, 36 was respectively (47 +/- 6), (126 +/- 13), (170 +/- 11) microm, all longer than those in BS group [(42 +/- 7), (98 +/- 14), (154 +/- 22) microm, with t values from 2.230 to 4.817, P < 0.05 or P < 0.01]. Cell migration distance in BS group at PSH 12, 24, 36, 48, 72 and B + I group at PSH 12, 24, 36, 48 was respectively shorter than that in B + I + M group (with t values respectively from 2.982 to 7.390 and 2.707 to 2.918, P < 0.05 or P < 0.01). (3) Cytomorphosis ability. Compared with those of C group, cell counts in lower compartment of BS group at PCH 4, 6, 8, 10, 12 were significantly decreased (with t values from -23.965 to -6.436, P values all below 0.01). Cell count in lower compartment of BS group at PCH 4, 6, 8, 10, 12 was respectively less than that of B + I group (with t values from 3.650 to 10.028, P values all below 0.01) and similar to that of B + M group (with t values from 0.199 to 0.797, P values all above 0.05). Cell counts in lower compartment of B + I + M group at PCH 4, 6, 8, 10, 12 were significantly larger than those of BS group (with t values from 4.313 to 15.100, P values all below 0.01). Cell count in lower compartment of B + I + M group at PCH 10 (328 +/- 47) and PCH 12 (465 +/- 37) was respectively larger than that in B + I group (277 +/- 25, 353 +/- 34, with t value respectively 3.051, 6.945, P values all below 0.01).
CONCLUSIONSITF can improve cytomorphosis ability for promoting cell migration with limited effect on cell proliferation, which can be enhanced with addition of mucin. The main mechanism of ITF in maintaining intestinal mucosal barrier may be attributed to acceleration of cell migration.
Animals ; Burns ; blood ; Cell Line ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Epithelial Cells ; cytology ; drug effects ; metabolism ; Intestinal Mucosa ; Intestines ; cytology ; metabolism ; Mucins ; pharmacology ; Peptides ; pharmacology ; Rats ; Serum ; immunology ; Trefoil Factor-2