IFN-γ Secreted by CD103+Dendritic Cells Leads to IgG Generation in the Mesenteric Lymph Node in the Absence of Vitamin A

The central nervous system (CNS) influences the immune system in a general fashion by regulating the systemic concentration of humoral substances, whereas the autonomic nervous system communicates specifically with the immune system according to local interactions. Data concerning the mechanisms of this bidirectional crosstalk of the peripheral nervous system (PNS) and immune system remain limited. To gain a better understanding of local interactions of the PNS and immune system, we have used immunofluorescent staining of glial fibrillary acidic protein (GFAP), coupled with confocal microscopy, to investigate the non-myelinating Schwann cell (NMSC)-immune cell interactions in mouse mesenteric lymph nodes. Our results demonstrate i) the presence of extensive NMSC processes and even of cell bodies in each compartment of the mouse mesenteric lymph node; ii) close associations/interactions of NMSC processes with blood vessels (including high endothelial venules) and the lymphatic vessel/sinus; iii) close contacts/associations of NMSC processes with various subsets of dendritic cells (such as CD4+CD11c+, CD8+CD11c+ dendritic cells), macrophages (F4/80+ and CD11b+ macrophages), and lymphocytes. Our novel findings concerning the distribution of NMSCs and NMSC-immune cell interactions inside the mouse lymph node should help to elucidate the mechanisms through which the PNS affects cellular- and humoral-mediated immune responses or vice versa in health and disease.

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Crucial roles of B7-H1 and B7-DC expressed on mesenteric lymph node dendritic cells in the generation of antigen-specific CD4+Foxp3+ regulatory T cells in the establishment of oral tolerance

Blood ◽

10.1182/blood-2009-10-250472 ◽

2010 ◽

Vol 116 (13) ◽

pp. 2266-2276 ◽

Cited By ~ 55

Author(s):

Tomohiro Fukaya ◽

Hideaki Takagi ◽

Yumiko Sato ◽

Kaori Sato ◽

Kawori Eizumi ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Lymph Node ◽

Regulatory T Cells ◽

Mesenteric Lymph Node ◽

Oral Tolerance ◽

Family Members ◽

T Cell Response ◽

Mesenteric Lymph ◽

B7 Family

Abstract Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to fed antigens. However, the molecular mechanism mediating oral tolerance remains unclear. In this study, we examined the role of the B7 family members of costimulatory molecules in the establishment of oral tolerance. Deficiencies of B7-H1 and B7-DC abrogated the oral tolerance, accompanied by enhanced antigen-specific CD4+ T-cell response and IgG1 production. Mesenteric lymph node (MLN) dendritic cells (DCs) displayed higher levels of B7-H1 and B7-DC than systemic DCs, whereas they showed similar levels of CD80, CD86, and B7-H2. MLN DCs enhanced the antigen-specific generation of CD4+Foxp3+ inducible regulatory T cells (iTregs) from CD4+Foxp3− T cells rather than CD4+ effector T cells (Teff) relative to systemic DCs, owing to the dominant expression of B7-H1 and B7-DC. Furthermore, the antigen-specific conversion of CD4+Foxp3− T cells into CD4+Foxp3+ iTregs occurred in MLNs greater than in peripheral organs during oral tolerance under steady-state conditions, and such conversion required B7-H1 and B7-DC more than other B7 family members, whereas it was severely impaired under inflammatory conditions. In conclusion, our findings suggest that B7-H1 and B7-DC expressed on MLN DCs are essential for establishing oral tolerance through the de novo generation of antigen-specific CD4+Foxp3+ iTregs.

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Protective Mucosal Th2 Immune Response against Toxoplasma gondii by Murine Mesenteric Lymph Node Dendritic Cells

Infection and Immunity ◽

10.1128/iai.71.9.5254-5265.2003 ◽

2003 ◽

Vol 71 (9) ◽

pp. 5254-5265 ◽

Cited By ~ 26

Author(s):

Isabelle Dimier-Poisson ◽

Fleur Aline ◽

Marie-Noëlle Mévélec ◽

Céline Beauvillain ◽

Dominique Buzoni-Gatel ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Lymph Node ◽

Toxoplasma Gondii ◽

Mesenteric Lymph Node ◽

Ex Vivo ◽

The Body ◽

Mouse Strains ◽

Mesenteric Lymph ◽

Th2 Immune Response

ABSTRACT Toxoplasma gondii, an obligate intracellular parasite pathogen which initially invades the intestinal epithelium before disseminating throughout the body, may cause severe sequelae in fetuses and life-threatening neuropathy in immunocompromised patients. Immune protection is usually thought to be performed through a systemic Th1 response; considering the route of parasite entry it is important to study and characterize the local mucosal immune response to T. gondii. Despite considerable effort, Toxoplasma-targeted vaccines have proven to be elusive using conventional strategies. We report the use of mesenteric lymph node dendritic cells (MLNDCs) pulsed ex vivo with T. gondii antigens (TAg) as a novel investigation approach to vaccination against T. gondii-driven pathogenic processes. Using a murine model, we demonstrate in two genetically distinct mouse strains (C57BL/6 and CBA/J) that adoptively transferred TAg-pulsed MLNDCs elicit a mucosal Toxoplasma-specific Th2-biased immune response in vivo and confer strong protection against infection. We also observe that MLNDCs mostly traffic to the intestine where they enhance resistance by reduction in the mortality and in the number of brain cysts. Thus, ex vivo TAg-pulsed MLNDCs represent a powerful tool for the study of protective immunity to T. gondii, delivered through its natural route of entry. These findings might impact the design of vaccine strategies against other invasive microorganisms known to be delivered through digestive tract.

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Oral Administration of EC-12 Increases the Baseline Gene Expression of Antiviral Cytokine Genes, IFN-γ and TNF-α, in Splenocytes and Mesenteric Lymph Node Cells of Weaning Piglets

Bioscience of Microbiota Food and Health ◽

10.12938/bmfh.32.123 ◽

2013 ◽

Vol 32 (4) ◽

pp. 123-128 ◽

Cited By ~ 1

Author(s):

Takeshi TSURUTA ◽

Ryo INOUE ◽

Toshiki TSUSHIMA ◽

Takumi WATANABE ◽

Takamitsu TSUKAHARA ◽

...

Keyword(s):

Gene Expression ◽

Lymph Node ◽

Oral Administration ◽

Mesenteric Lymph Node ◽

Cytokine Genes ◽

Mesenteric Lymph ◽

Tnf Α ◽

Lymph Node Cells ◽

Ifn Γ ◽

Weaning Piglets

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Cyclopia Extracts Enhance Th1-, Th2-, and Th17-type T Cell Responses and Induce Foxp3+ Cells in Murine Cell Culture

Planta Medica ◽

10.1055/s-0043-121270 ◽

2017 ◽

Vol 84 (05) ◽

pp. 311-319 ◽

Cited By ~ 5

Author(s):

Shiho Murakami ◽

Yutaka Miura ◽

Makoto Hattori ◽

Hiroshi Matsuda ◽

Christiaan Malherbe ◽

...

Keyword(s):

Lymph Node ◽

Mesenteric Lymph Node ◽

Hot Water ◽

Immunostimulatory Activity ◽

Murine Splenocytes ◽

Enhanced Production ◽

Mesenteric Lymph ◽

Lymph Node Cells ◽

Ifn Γ

Abstract Cyclopia genistoides, one of the traditional South African medicinal plants, and other species of the same genus offer noteworthy phenolic profiles, in particular high levels of the anti-allergic xanthone mangiferin. Hot water and 40% ethanol-water (v/v) extracts, prepared from C. genistoides, Cyclopia subternata, and Cyclopia maculata, were tested for immune-regulating activity in vitro using murine splenocytes and mesenteric lymph node cells. The 40% ethanol-water extracts of C. genistoides and C. subternata significantly enhanced production of several types of cytokines, including IL-4, IL-17, and IFN-γ, by antigen-stimulated splenocytes. A concentration-dependent response was observed, noticeably for IFN-γ production. The activity of the extracts did not correlate with the content of any of the major phenolic compounds, indicative that other extract constituents also play a role in immunomodulation. Additionally, the increased ratio of CD4+CD25+Foxp3+ Treg cells to total CD4+ cells indicated induction of Foxp3+ cells when mesenteric lymph node cells were cultured in the presence of these two extracts. This study is the first reporting immunostimulatory activity for Cyclopia, which are widely consumed as the herbal tea known as honeybush, underpinning further investigations into the potential use of its extracts as adjuvants for mucosal immunotherapy.

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Influences of orally administered lactoferrin on IFN-γ and IL-10 production by intestinal intraepithelial lymphocytes and mesenteric lymph-node cellsThis paper is one of a selection of papers published in this Special Issue, entitled 7th International Conference on Lactoferrin: Structure, Function, and Applications, and has undergone the Journal's usual peer review process.

Biochemistry and Cell Biology ◽

10.1139/o06-056 ◽

2006 ◽

Vol 84 (3) ◽

pp. 363-368 ◽

Cited By ~ 30

Author(s):

Natsuko Takakura ◽

Hiroyuki Wakabayashi ◽

Koji Yamauchi ◽

Mitsunori Takase

Keyword(s):

Lymph Node ◽

T Cell ◽

T Cell Receptor ◽

Mesenteric Lymph Node ◽

Cell Receptor ◽

Intraepithelial Lymphocytes ◽

Bovine Lactoferrin ◽

Intestinal Intraepithelial Lymphocytes ◽

Mesenteric Lymph ◽

Ifn Γ

Intestinal mucosal immunity plays an important role in mucosal and systemic immune responses. We investigated the influences of orally administered bovine lactoferrin (LF) on cytokine production by intestinal intraepithelial lymphocytes (IEL) and mesenteric lymph-node (MLN) cells, especially T cells. Bovine LF or bovine serum albumin (control) was administered to mice once daily for 3 d. After 24 h from the last administration, IEL of the jejunum and ileum and MLN cells were isolated. These cells were cultured with and without the anti-T-cell-receptor antibody, and then the culture supernatants were assayed for cytokines with ELISA. Oral LF did not affect the ratio of T-cell subpopulations in IEL and MLN; however, LF enhanced both interferon (IFN)-γ and interleukin (IL)-10 production by unstimulated IEL and by IEL stimulated with the αβ T-cell receptor but not with the γδ T-cell receptor. LF also enhanced both IFN-γ and IL-10 production by stimulated and unstimulated MLN cells. The production level of IFN-γ by MLN cells was correlated with that of IL-10. These results suggest that oral LF enhances the production of both Th1-type and Th2/Tr-type cytokines in the small intestine of healthy animals.

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Interleukin-23: Linking Mesenteric Lymph Node Dendritic Cells With Th1 Immunity in Crohn's Disease

Gastroenterology ◽

10.1053/j.gastro.2009.09.029 ◽

2009 ◽

Vol 137 (5) ◽

pp. 1566-1570 ◽

Cited By ~ 1

Author(s):

Maria Rescigno ◽

Iliyan D. Iliev

Keyword(s):

Dendritic Cells ◽

Crohn’S Disease ◽

Lymph Node ◽

Crohn's Disease ◽

Mesenteric Lymph Node ◽

Mesenteric Lymph ◽

Interleukin 23

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Immunity to Trichinella spiralis infection in vitamin A-deficient mice.

Journal of Experimental Medicine ◽

10.1084/jem.175.1.111 ◽

1992 ◽

Vol 175 (1) ◽

pp. 111-120 ◽

Cited By ~ 60

Author(s):

J A Carman ◽

L Pond ◽

F Nashold ◽

D L Wassom ◽

C E Hayes

Keyword(s):

Lymph Node ◽

Vitamin A ◽

Mesenteric Lymph Node ◽

Trichinella Spiralis ◽

Natural Infection ◽

Ifn Gamma ◽

Transcript Levels ◽

Mesenteric Lymph ◽

A Cells ◽

Deficient Mice

Vitamin A-deficient (A-) mice make strikingly poor IgG responses when they are immunized with purified protein antigens. Previously, we showed that A- T cells overproduce interferon gamma (IFN-gamma), which then could inhibit interleukin 4 (IL-4)-stimulated B cell IgG responses. To determine if the altered IFN-gamma regulation pattern and its immunological consequences would extend to a natural infection, we studied mice infected with the parasitic helminth Trichinella spiralis. The course of the infection was similar in A- and A-sufficient (A+) mice. These mice did not differ with respect to newborn larvae/female/hour produced in the intestine, or muscle larvae burden 5 wk postinfection. They also did not differ in the intestinal worm expulsion rate until day 15, when A- mice still harbored parasites, whereas A+ mice had cleared intestinal worms. Vitamin A deficiency reduced both the frequency of B lymphocytes secreting IgG1 antibodies to parasite antigens, and the bone marrow eosinophilia associated with helminth infection. The cytokine secretion patterns in infected mice were consistent with these observations and with previous studies. Mesenteric lymph node cells from infected A- mice secreted significantly more IFN-gamma, and significantly less IL-2, IL-4, and IL-5 than infected A+ controls. A- splenocytes secreted significantly more IFN-gamma, and equivalent amounts of IL-2, IL-4, and IL-5 compared with A+ controls. Interestingly, CD4-CD8- cells secreted the majority of the IL-4 produced in the spleen. The IL-2, IL-4, and IL-5 steady-state transcript levels correlated with secreted protein levels, but IFN-gamma transcripts did not. Although they secreted more protein, A- cells contained fewer IFN-gamma transcripts than A+ cells. These results suggest two vitamin A-mediated regulation steps in IFN-gamma gene expression: positive regulation of IFN-gamma transcript levels, and negative regulation posttranscriptionally. The essentially unaltered outcome of T. spiralis infection in vitamin A-deficient mice probably reflects a balance between cellular and humoral responses. The IFN-gamma overproduction might have a positive effect on the gut inflammatory response, but the decrease eosinophilia, cytokine production in mesenteric lymph node, and IgG1-secreting cell frequency might have a negative effect on T. spiralis immunity.

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