Transcriptional profiling of stroma from inflamed and resting lymph nodes defines immunological hallmarks

Abstract

Lymph node stromal cells (LNSCs) closely regulate immunity and self-tolerance, yet key aspects of their biology remain poorly illuminated. Comparative transcriptomic analyses of murine LNSC subsets revealed expression of important immune mediators, growth factors, and novel structural components. Pairwise analyses of ligands and cognate receptors across hematopoietic and stromal subsets suggested a complex web of cross-talk. Compared with skin and thymic fibroblasts, fibroblastic reticular cells (FRCs) were enriched in genes relevant to cytokine signaling. LNSCs from inflamed lymph nodes upregulated acute phase response genes, chemokines, and antigen presentation genes. Poorly studied podoplanin−CD31− LNSCs showed similarities to FRCs, but lacked IL-7 expression, and were identified as myofibroblastic integrin α7+ pericytes. Together these data comprehensively describe the transcriptional characteristics of LNSC subsets.

Immunomodulatory Roles of Lymphatic Vessels in Cancer Progression

“…Without CCR7, DCs are unable to home to the lymph node after activation (30). LECs also express adhesion molecules such as ICAM-1 and e-selectin to facilitate DC transmigration, and LECs can modulate their expression of CCL21, ICAM-1, and e-selectin, among other cellsurface molecules, according to inflammatory cues (31). One such inflammatory cue is interstitial flow, which is rapidly upregulated upon cellular insult or injury (i.e., within seconds, due to rapid onset of capillary leakiness).…”

Defective Stromal Remodeling and Neutrophil Extracellular Traps in Lymphoid Tissues Favor the Transition from Autoimmunity to Lymphoma

“…In SLO, SPARC is a determinant of correct germinal center assembly and lymphocyte traffi cking during adaptive immune responses ( 19 ). Accordingly, the transcriptional profi le of the stroma of SLO responding to infection shows high SPARC expression ( 20 ).…”

Fibroblastic reticular cells of the lymph node are required for retention of resting but not activated CD8 + T cells

“…Moreover, our understanding of whether FRCs similarly regulate the retention in the LNs of activated T cells is even less complete. That FRCs participate in an active immune response is suggested by the transcriptional changes that they exhibit in response to inflammation (8), the role of stromal-derived retinoic acid in promoting expression of gut-homing integrins by T cells (9), and by the proposal that their "maturation" may be required for the generation of antiviral immune responses (10). Recent studies have also suggested that LN FRCs suppress T-cell proliferation through their expression of Nos2 in response to T-cell-derived interferon (IFN)-γ (11-13).…”