CXCR5‐ and CCR7‐dependent lymphoid neogenesis in a murine model of chronic antigen‐induced arthritis

Wengner, Antje M.; Höpken, Uta E.; Petrow, Peter; Hartmann, Sven; Schurigt, Uta; Bräuer, Rolf; Lipp, Martin

doi:10.1002/art.22939

Cited by 96 publications

(73 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, CXCR5 and CCR7, the receptors for CXCL13 and CCL19, respectively, appear to be important for lymphoid neogenesis in chronic inflammatory autoimmune disease [30]. In contrast, the inability of LTa -/-mice to generate a CXCL13-and CCL19-response does not prevent the development of pulmonary lymphoid aggregates upon chronic CS exposure, suggesting other chemokines are involved.…”

Section: Discussionmentioning

confidence: 98%

Role of lymphotoxin- in cigarette smoke-induced inflammation and lymphoid neogenesis

Demoor¹,

Bracke²,

Maes³

et al. 2009

European Respiratory Journal

View full text Add to dashboard Cite

In chronic obstructive pulmonary disease (COPD), chronic inflammation is accompanied by peribronchial lymphoid aggregates. Lymphotoxin (LT)-a, crucial in secondary lymphoid organogenesis, may be involved in lymphoid neogenesis.We examined cigarette smoke (CS)-induced pulmonary lymphoid neogenesis and inflammation in vivo in LTa knockout (LTa -/-) and wild-type (WT) mice and studied the expression of lymphoid chemokines by lung fibroblasts in vitro.T-cell numbers (in bronchoalveolar lavage fluid (BALF) and lungs) and lymphoid aggregate numbers were significantly higher in air-exposed LTa -/-mice than in WT animals, and increased upon chronic CS exposure in both genotypes. In contrast, local immunoglobulin A responses upon chronic CS exposure were attenuated in LTa , lung fibroblasts. In this murine model of COPD, CS induces pulmonary expression of lymphoid chemokines CXCL13 and CCL19 in a LTab-LTbR-dependent fashion. However, LTa is not required for CSinduced pulmonary lymphocyte accumulation and neogenesis of lymphoid aggregates.

show abstract

Section: Discussionmentioning

confidence: 98%

Role of lymphotoxin- in cigarette smoke-induced inflammation and lymphoid neogenesis

Demoor¹,

Bracke²,

Maes³

et al. 2009

European Respiratory Journal

View full text Add to dashboard Cite

show abstract

“…Conventional immunohistochemistry was performed as described previously. 21 For immunofluorescence, sections were blocked for 30 minutes with 10% normal mouse or goat serum, respectively, and slides were stained for 1.5 hours at room temperature with biotinylated or fluorescently labeled antibodies. For indirect staining, secondary labeled antibodies were incubated for 1 hour.…”

Section: Immunohistologymentioning

confidence: 99%

Cooperative function of CCR7 and lymphotoxin in the formation of a lymphoma-permissive niche within murine secondary lymphoid organs

Rehm

Mensen

Schradi

et al. 2011

Blood

Self Cite

View full text Add to dashboard Cite

Lymphoma cell survival and progression are putatively dependent on a specific microanatomic localization within secondary lymphoid organs. Despite compelling data correlating homeostatic chemokine receptor expression and human lymphoma pathogenesis, genetic models that either mimic lymphoma dissemination or dissect a crosstalk of lymphoma and stromal cells are missing. Applying the genetically tractable EMyc transgenic mouse model, we show that the chemokine receptor CCR7 regulates EMyc lymphoma homing to lymph nodes and distinctive microanatomic sites of the spleen. CCR7-controlled access of lymphoma cells to the splenic T-cell zone led to a significant survival advantage compared with CCR7-deficient lymphoma cells, which were excluded from this zone. Within the niche, lymphoma cells stimulated a reciprocal cross-talk with gp38 ؉ fibroblastic reticular cells. This reciprocal cooperation program was mediated by lymphoma B cellpresented lymphotoxin, which acted on lymphotoxin-␤-receptor-bearing stromal cells followed by alteration of stromal cellular composition. Cross-talk inhibition by lymphotoxin-␣ deletion and using a lymphotoxin-␤ receptor-immunoglobulin fusion protein impaired lymphoma growth. Thus, abrogation of CCR7-governed migration and of sustained lymphotoxin signaling could provide new targets in lymphoma therapy. (Blood. 2011;118(4):1020-1033) IntroductionThe crosstalk between lymphoid tumor cells and their microenvironment provides pivotal signals for the localization and progression of lymphoid malignancies. Thus, it has become increasingly important to define which molecular mechanisms allow the interactions between accessory cells and malignant B-cells and to identify the stromal cells that mediate such signals. 1,2 In E-Myc transgenic mice, a mouse model of Myc-driven aggressive human B-cell lymphoma, the precancerous state is characterized by excessive proliferation in conjunction with the onset of an apoptotic program within the bone marrow precursor and immature B-cell compartment. 3,4 Although the role of genetic lesions as steps toward cell autonomy and tumor growth has been appreciated, 5,6 in vivo the conditions for lymphoma cell lodging within secondary lymphoid organs (SLOs) remain to be addressed. Several in vitro studies or transfer models of human lymphoma cell lines into immunodeficient mice could demonstrate that a variety of cytokines, adhesion molecules, and growth factors were involved in the cross-talk at the stroma-lymphoma cell interface. 7,8 Clinical studies have correlated the involvement of chemokine receptors with nodal homing of B-cell non-Hodgkin (NHL) and Hodgkin lymphoma. 9,10 Conversely, lack of the major lymph node (LN) addressins, foremost the homeostatic chemokine receptors CXCR5 and CCR7, may predispose those tumor cells for extranodal dissemination instead. 11 In vivo, the dissemination of primary central nervous system lymphoma toward brain-expressed chemokine ligand CCL21 has been shown to be controlled by CCR7 expression. 12 Although this investigation consi...

show abstract

“…Chronic AIA was induced, as described earlier (17). C57BL/6 mice were immunized on day 221 with a s.c. injection of 100 mg methylated BSA (mBSA; Sigma-Aldrich, St. Louis, MO) in 50 ml PBS emulsified in 50 ml CFA (Sigma-Aldrich) and supplemented with 4 mg/ml heat-killed Mycobacterium tuberculosis strain H37RA (Difco, Detroit, MI).…”

Section: Chronic Aiamentioning

confidence: 99%

Experimental Arthritis Triggers Periodontal Disease in Mice: Involvement of TNF-α and the Oral Microbiota

Queiroz-Junior

Madeira

Coelho

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) and periodontal disease (PD) are prevalent chronic inflammatory disorders that affect bone structures. Individuals with RA are more likely to experience PD, but how disease in joints could induce PD remains unknown. This study aimed to experimentally mimic clinical parameters of RA-induced PD and to provide mechanistic findings to explain this association. Chronic Ag-induced arthritis (AIA) was triggered by injection of methylated BSA in the knee joint of immunized mice. Anti–TNF-α was used to assess the role of this cytokine. Intra-articular challenge induced infiltration of cells, synovial hyperplasia, bone resorption, proteoglycan loss, and increased expression of cytokines exclusively in challenged joints. Simultaneously, AIA resulted in severe alveolar bone loss, migration of osteoclasts, and release of proinflammatory cytokines in maxillae. Anti–TNF-α therapy prevented the development of both AIA and PD. AIA did not modify bacterial counts in the oral cavity. PD, but not AIA, induced by injection of Ag in immunized mice was decreased by local treatment with antiseptic, which decreased the oral microbiota. AIA was associated with an increase in serum C-reactive protein levels and the expression of the transcription factors RORγ and Foxp3 in cervical lymph nodes. There were higher titers of anti-collagen I IgG, and splenocytes were more responsive to collagen I in AIA mice. In conclusion, AIA-induced PD was dependent on TNF-α and the oral microbiota. Moreover, PD was associated with changes in expression of lymphocyte transcription factors, presence of anti-collagen Abs, and increased reactivity to autoantigens.

show abstract

CXCR5‐ and CCR7‐dependent lymphoid neogenesis in a murine model of chronic antigen‐induced arthritis

Cited by 96 publications

References 52 publications

Role of lymphotoxin- in cigarette smoke-induced inflammation and lymphoid neogenesis

Role of lymphotoxin- in cigarette smoke-induced inflammation and lymphoid neogenesis

Cooperative function of CCR7 and lymphotoxin in the formation of a lymphoma-permissive niche within murine secondary lymphoid organs

Experimental Arthritis Triggers Periodontal Disease in Mice: Involvement of TNF-α and the Oral Microbiota

Contact Info

Product

Resources

About