Disrupted Lymph Node and Splenic Stroma in Mice with Induced Inflammatory Melanomas Is Associated with Impaired Recruitment of T and Dendritic Cells

Soudja, Saïdi M.; Henri, Sandrine; Mello, Marielle; Chasson, Lionel; Mas, Amandine; Wehbe, Maria; Auphan-Anezin, Nathalie; Leserman, Lee; Eynde, Benoı̂t Van den; Schmitt-Verhulst, Anne-Marie

doi:10.1371/journal.pone.0022639

Cited by 29 publications

(22 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Restoration of the LN structure is necessary for regaining immunocompetence (66). Chronic inflammation in tumor-draining LNs results in a disruption of the stromal network and loss of T-cell-zone FRCs, leading to a decrease in CCL21 and a reduced T cell influx to the LNs (67). Our work demonstrated that LN remodeling also occurred acutely following tolerance induction.…”

Section: Days) Data Presented As Mean ± Sem (A-d) or Percent Survivamentioning

confidence: 61%

Laminins affect T cell trafficking and allograft fate

Warren¹,

Iwami²,

Harris³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

Lymph nodes (LNs) are integral sites for the generation of immune tolerance, migration of CD4 + T cells, and induction of Tregs. Despite the importance of LNs in regulation of inflammatory responses, the LN-specific factors that regulate T cell migration and the precise LN structural domains in which differentiation occurs remain undefined. Using intravital and fluorescent microscopy, we found that alloreactive T cells traffic distinctly into the tolerant LN and colocalize in exclusive regions with alloantigen-presenting cells, a process required for Treg induction. Extracellular matrix proteins, including those of the laminin family, formed regions within the LN that were permissive for colocalization of alloantigen-presenting cells, alloreactive T cells, and Tregs. We identified unique expression patterns of laminin proteins in high endothelial venule basement membranes and the cortical ridge that correlated with alloantigen-specific immunity or immune tolerance. The ratio of laminin α4 to laminin α5 was greater in domains within tolerant LNs, compared with immune LNs, and blocking laminin α4 function or inducing laminin α5 overexpression disrupted T cell and DC localization and transmigration through tolerant LNs. Furthermore, reducing α4 laminin circumvented tolerance induction and induced cardiac allograft inflammation and rejection in murine models. This work identifies laminins as potential targets for immune modulation.

show abstract

Section: Days) Data Presented As Mean ± Sem (A-d) or Percent Survivamentioning

confidence: 61%

Laminins affect T cell trafficking and allograft fate

Warren¹,

Iwami²,

Harris³

et al. 2014

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…[24] This immunosuppression occurs even in the absence of sentinel-node involvement[25], suggesting that it may be partly mediated by the release of different cytokines from the primary tumor. [26–29]…”

Section: Discussionmentioning

confidence: 99%

Effect of time to sentinel-node biopsy on the prognosis of cutaneous melanoma

Tejera‐Vaquerizo

Nagore

Puig

et al. 2015

European Journal of Cancer

View full text Add to dashboard Cite

Instroduction In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumor and sentinel-node biopsy. The objective of this study is to analyze the prognostic implications of this delay. Patients and method This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival. Results A delay time of 40 days or less (HR, 1.7; CI, 1.2 to 2.5) increased Breslow thickness (Breslow ≥2 mm, HR >3.7; CI 1.4 to 10.7), ulceration (HR 1.6; CI, 1.1 to 2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9 to 4.2), and primary melanoma localized in the head or neck were independently associated with worse melanoma-specific survival (all P<0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression. Conclusion Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma.

show abstract

“…This network is, in part, comprised of the stromal fiber ER-TR7 secreted by FRC (19) and the disruption of this network results in insufficient or improper immune responses to immune challenge (12, 30–32). FRC build, remodel, and maintain the fiber network that gives the LN shape, defines microdomains within the LN, and provides a platform and directional cues via cytokines and chemokines for lymphocyte migration (19, 33, 34).…”

Section: Discussionmentioning

confidence: 99%

Lymph Node Stromal Fiber ER-TR7 Modulates CD4+ T Cell Lymph Node Trafficking and Transplant Tolerance

et al. 2015

View full text Add to dashboard Cite

Background Trafficking and differentiation of naïve CD4+ and regulatory T cells (Treg) within the lymph node (LN) are integral for tolerance induction. The LN is comprised of stromal fibers that dictate lymphocyte migration and LN structure, organization, and microanatomic domains. Distribution of the stromal fiber ER-TR7 changes within the LN following antigenic challenge, but the contributions of ER-TR7 to the resulting immune response remain undefined. We hypothesized that these stromal fiber structural changes affect T cell fate and subsequently allograft survival. Methods C57BL/6 mice were left naïve (untreated) or made immune or tolerant (donor-specific BALB/c splenocyte transfusion −/+ anti-CD40L mAb), or made tolerant and received anti-ER-TR7 mAb. Donor-specific T cell migration was visualized by adoptive transfer of CFSE-labeled TEa T cell receptor transgenic CD4+ cells. Immunohistochemistry was performed on lymph nodes to detect stromal fiber distribution, structure, CCL21 presence, and Treg and donor-specific cell location relative to high endothelial venules (HEV). Naïve, tolerant, and tolerant + anti-ER-TR7 mice received BALB/c heterotopic cardiac allografts and graft survival was monitored. Results ER-TR7 distribution changed following the induction of tolerance vs. immunity. Treating tolerant mice with anti-ER-TR7 altered HEV basement membrane structure and the distribution of CCL21 within the LN. These differences were mirrored by changes in the migration of naïve and Treg cells within and surrounding the HEV. Anti-ER-TR7 prevented tolerance induction and resulted in allograft inflammation and rejection. Conclusions These results identify ER-TR7 as an important component of LN structure in tolerance and a direct target for immune modulation.

show abstract

Disrupted Lymph Node and Splenic Stroma in Mice with Induced Inflammatory Melanomas Is Associated with Impaired Recruitment of T and Dendritic Cells

Cited by 29 publications

References 48 publications

Laminins affect T cell trafficking and allograft fate

Laminins affect T cell trafficking and allograft fate

Effect of time to sentinel-node biopsy on the prognosis of cutaneous melanoma

Lymph Node Stromal Fiber ER-TR7 Modulates CD4+ T Cell Lymph Node Trafficking and Transplant Tolerance

Contact Info

Product

Resources

About