Lymph Node Stromal Cells From Different Draining Areas Distinctly Regulate the Development of Chronic Intestinal Inflammation

The balance between the responsiveness of the intestinal immune system and the gut environment is fundamental for the maintenance of intestinal homeostasis, which is required for an adequate recognition of entering antigens. The disruption of this homeostasis by exaggerated immune response to harmless antigens can lead to the development of intestinal disorders such as inflammatory bowel disease. Stromal cells are sessile non-hematopoietic cells that build the backbone of the lymph node, an important site for the immune response induction, but also contribute to immune response and tolerance induction. However, the knowledge about the role of stromal cells in the regulation of inflammatory responses is still limited. Therefore, in this study we analyzed the influence of stromal cells on the development of chronic intestinal inflammation. Here, we show that intestinal inflammation alters the immune activation of the mesenteric lymph node-derived stromal cells. Podoplanin+ and CD21/35+ stromal cells showed increased expression of MHC class II molecules, but CD106 expression on CD21/35+ cells was reduced. Stromal cells secreted cytokines and chemokines such as CCL7 and CXCL16 influenced the gut-homing phenotype and proliferation of CD4+ and CD8+ T cells. Furthermore, stromal cells of peripheral lymph nodes transplanted into the mesentery attenuated colitis severity in B6-Il10-/- mice. The reduced colitis severity in these mice was associated with increased expression of IL4 and distinct activation pattern of stromal cells derived from transplanted peripheral lymph nodes. Altogether, our results demonstrate that lymph node stromal cells impact development of chronic colitis via T cell induction. Moreover, lymph node stromal cells from different draining area due to neonatally imprinted processes distinctly regulate the induction of immune responses.

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Peripheral lymph node stromal cells can promote growth and tumorigenicity of breast carcinoma cells through the release of IGF-I and EGF

International Journal of Cancer ◽

10.1002/ijc.10481 ◽

2002 ◽

Vol 100 (1) ◽

pp. 2-8 ◽

Cited By ~ 43

Author(s):

Christina LeBedis ◽

Keguan Chen ◽

Lucia Fallavollita ◽

Tarek Boutros ◽

Pnina Brodt

Keyword(s):

Lymph Node ◽

Breast Carcinoma ◽

Stromal Cells ◽

Carcinoma Cells ◽

Peripheral Lymph Node ◽

Breast Carcinoma Cells ◽

Peripheral Lymph ◽

Igf I ◽

Lymph Node Stromal Cells

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Lymph node stromal cells strongly influence immune response suppression

European Journal of Immunology ◽

10.1002/eji.201040681 ◽

2011 ◽

Vol 41 (3) ◽

pp. 624-633 ◽

Cited By ~ 7

Author(s):

Manuela Buettner ◽

Reinhard Pabst ◽

Ulrike Bode

Keyword(s):

Immune Response ◽

Lymph Node ◽

Stromal Cells ◽

Response Suppression ◽

Lymph Node Stromal Cells

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Role of NF-κB in immune and inflammatory responses in the gut

Gut ◽

10.1136/gut.43.6.856 ◽

1998 ◽

Vol 43 (6) ◽

pp. 856-860 ◽

Cited By ~ 228

Author(s):

M F NEURATH ◽

C BECKER ◽

K BARBULESCU

Keyword(s):

Intestinal Inflammation ◽

Inflammatory Responses ◽

Proteasome Inhibitors ◽

Treatment Strategies ◽

Expression Vectors ◽

Surface Receptors ◽

Intestinal Immune System ◽

Inflammatory Bowel ◽

New Treatment ◽

Chronic Intestinal Inflammation

NF-κB is a pleiotropic transcription factor with key functions in the intestinal immune system. NF-κB family members control transcriptional activity of various promoters of proinflammatory cytokines, cell surface receptors, transcription factors, and adhesion molecules that are involved in intestinal inflammation. The perpetuated activation of NF-κB in patients with active inflammatory bowel disease suggests that regulation of NF-κB activity is a very attractive target for therapeutic intervention. Such strategies include antioxidants, proteasome inhibitors, inhibition of NF-κB by adenoviral IκBα expression vectors, and antisense DNA targeting of NF-κB. These approaches will hopefully permit the design of new treatment strategies for chronic intestinal inflammation.

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Faculty Opinions recommendation of Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725241262.793528884 ◽

2017 ◽

Author(s):

Theresa Lu ◽

William Shipman ◽

Dragos Dasoveanu

Keyword(s):

Lymph Node ◽

Antigen Presentation ◽

Mhc Class Ii ◽

Stromal Cells ◽

Class Ii ◽

Self Antigen ◽

Lymph Node Stromal Cells

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Salmonella Persistence within the Peripheral Lymph Nodes of Cattle following Experimental Inoculation

Journal of Food Protection ◽

10.4315/0362-028x.jfp-15-325 ◽

2016 ◽

Vol 79 (6) ◽

pp. 1032-1035 ◽

Cited By ~ 6

Author(s):

T. S. EDRINGTON ◽

G. H. LONERAGAN ◽

K. J. GENOVESE ◽

D. L. HANSON ◽

D. J. NISBET

Keyword(s):

Body Weight ◽

Lymph Node ◽

Lymph Nodes ◽

Enrichment Culture ◽

Lower Leg ◽

Challenge Strain ◽

Peripheral Lymph ◽

Experimental Inoculation ◽

Duration Of Infection

ABSTRACT Utilizing a transdermal method of inoculation developed in our laboratory, the duration of infection of Salmonella in the peripheral lymph nodes of steers was examined. Thirty-six Holstein steers (mean body weight of 137 kg) were inoculated with Salmonella Montevideo (day 0) on each lower leg and both sides of the back and abdomen. Calves were euthanized beginning at 6 h and subsequently on each of days 1, 2, 4, 7, 9, 11, 14, and 21 postinoculation (four animals each time). The subiliac, popliteal, and superficial cervical (prescapular) lymph nodes were collected and cultured (quantitatively and qualitatively) for the challenge strain of Salmonella. The challenge strain was detected via direct culture within the lymph nodes at 6 h postinoculation and on each subsequent necropsy date. Salmonella levels in lymph node were 0.8 to 1.8 log CFU/g. Lymph nodes were generally positive after enrichment culture throughout the experiment. Salmonella elimination appeared to begin approximately 14 days postinoculation. However, elimination was not completed by day 21; therefore, a second experiment was conducted identical to the first except that the time from inoculation to necropsy was extended. Salmonella was recovered via direct culture on each of the necropsy days, and results in general were similar to those of experiment I, except that on days 20, 24, and 28 isolates from serogroups C2 and E1 were identified in addition to the inoculation strain C1 in multiple animals. The data from both experiments indicate that after a single inoculation event, Salmonella would be completely cleared by approximately 28 days. Further research with expanded times between inoculation and necropsy is required for verification.

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Lymph node stromal cells constrain immunity via MHC class II self-antigen presentation

eLife ◽

10.7554/elife.04433 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 45

Author(s):

Antonio P Baptista ◽

Ramon Roozendaal ◽

Rogier M Reijmers ◽

Jasper J Koning ◽

Wendy W Unger ◽

...

Keyword(s):

T Cells ◽

Lymph Node ◽

Antigen Presentation ◽

Mhc Class Ii ◽

Cd8 T Cells ◽

Stromal Cells ◽

Transplant Rejection ◽

Mhc Ii ◽

Self Antigen ◽

Lymph Node Stromal Cells

Non-hematopoietic lymph node stromal cells shape immunity by inducing MHC-I-dependent deletion of self-reactive CD8+ T cells and MHC-II-dependent anergy of CD4+ T cells. In this study, we show that MHC-II expression on lymph node stromal cells is additionally required for homeostatic maintenance of regulatory T cells (Tregs) and maintenance of immune quiescence. In the absence of MHC-II expression in lymph node transplants, i.e. on lymph node stromal cells, CD4+ as well as CD8+ T cells became activated, ultimately resulting in transplant rejection. MHC-II self-antigen presentation by lymph node stromal cells allowed the non-proliferative maintenance of antigen-specific Tregs and constrained antigen-specific immunity. Altogether, our results reveal a novel mechanism by which lymph node stromal cells regulate peripheral immunity.

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OP0256 Changes of Microrna Expression in Lymph Node Stromal Cells of Rheumatoid Arthritis Patients

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-eular.4383 ◽

2014 ◽

Vol 73 (Suppl 2) ◽

pp. 158.2-158

Author(s):

C. Ospelt ◽

J. Hähnlein ◽

R.E. Gay ◽

P.P. Tak ◽

D.M. Gerlag ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Lymph Node ◽

Stromal Cells ◽

Microrna Expression ◽

Lymph Node Stromal Cells

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CD44-dependent lymphoma cell dissemination: a cell surface CD44 variant, rather than standard CD44, supports in vitro lymphoma cell rolling on hyaluronic acid substrate and its in vivo accumulation in the peripheral lymph nodes

Journal of Cell Science ◽

10.1242/jcs.114.19.3463 ◽

2001 ◽

Vol 114 (19) ◽

pp. 3463-3477

Author(s):

Shulamit B. Wallach-Dayan ◽

Valentin Grabovsky ◽

Jürgen Moll ◽

Jonathan Sleeman ◽

Peter Herrlich ◽

...

Keyword(s):

Cell Migration ◽

Hyaluronic Acid ◽

Lymph Node ◽

Cell Surface ◽

Lymph Nodes ◽

Local Tumor ◽

Cd44 Variant ◽

Peripheral Lymph

Cell motility is an essential element of tumor dissemination, allowing organ infiltration by cancer cells. Using mouse LB lymphoma cells transfected with standard CD44 (CD44s) cDNA (LB-TRs cells) or with the alternatively spliced CD44 variant CD44v4-v10 (CD44v) cDNA (LB-TRv cells), we explored their CD44-dependent cell migration. LB-TRv cells, but not LB-TRs or parental LB cells, bound soluble hyaluronic acid (HA) and other glycosaminoglycans (GAGs), and exclusively formed, under physiological shear force, rolling attachments on HA substrate. Furthermore, LB-TRv cells, but not LB-TRs cells or their parental LB cells, displayed accelerated local tumor formation and enhanced accumulation in the peripheral lymph nodes after s.c. inoculation. The aggressive metastatic behavior of i.v.-injected LB-TRV cells, when compared with that of other LB-transfectants, is attributed to more efficient migration to the lymph nodes, rather than to local growth in the lymph node. Injection of anti-CD44 monoclonal antibody or of the enzyme hyaluronidase also prevented tumor growth in lymph nodes of BALB/c mice inoculated with LB-TRv cells. The enhanced in vitro rolling and enhanced in vivo local tumor growth and lymph node invasion disappeared in LB cells transfected with CD44v cDNA bearing a point mutation at the HA binding site, located at the distal end of the molecule constant region. These findings show that the interaction of cell surface CD44v with HA promotes cell migration both in vitro and in vivo, and they contribute to our understanding of the mechanism of cell trafficking, including tumor spread.

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