title: 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 elucidated. Here, comparative transcriptomic analyses of mouse LNSC subsets demonstrated the expression of important immune mediators, growth factors and previously unknown structural components. Pairwise analyses of ligands and cognate receptors across hematopoietic and stromal subsets suggested a complex web of crosstalk. Fibroblastic reticular cells (FRCs) showed enrichment for higher expression of genes relevant to cytokine signaling, relative to their expression in skin and thymic fibroblasts. LNSCs from inflamed lymph nodes upregulated expression of genes encoding chemokines and molecules involved in the acute-phase response and the antigen-processing and antigen-presentation machinery. Poorly studied podoplanin (gp38)-negative CD31(-) LNSCs showed similarities to FRCs but lacked expression of interleukin 7 (IL-7) and were identified as myofibroblastic pericytes that expressed integrin α(7). Together our data comprehensively describe the transcriptional characteristics of LNSC subsets.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Deepali
authors.initials: D
authors.lastname: Malhotra
authors.forename: Anne L
authors.initials: AL
authors.lastname: Fletcher
authors.forename: Jillian
authors.initials: J
authors.lastname: Astarita
authors.forename: Veronika
authors.initials: V
authors.lastname: Lukacs-Kornek
authors.forename: Prakriti
authors.initials: P
authors.lastname: Tayalia
authors.forename: Santiago F
authors.initials: SF
authors.lastname: Gonzalez
authors.forename: Kutlu G
authors.initials: KG
authors.lastname: Elpek
authors.forename: Sook Kyung
authors.initials: SK
authors.lastname: Chang
authors.forename: Konstantin
authors.initials: K
authors.lastname: Knoblich
authors.forename: Martin E
authors.initials: ME
authors.lastname: Hemler
authors.forename: Michael B
authors.initials: MB
authors.lastname: Brenner
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Turley
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology*; D006706:Homeostasis / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D039001:Integrin alpha Chains / Q000276:immunology / Q000378:metabolism; D015851:Interleukin-7 / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020286:Pericytes / Q000276:immunology / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology* / Q000378:metabolism*; D046888:Tissue Array Analysis / Q000379:methods; D059467:Transcriptome; D000098853:Podoplanin
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D039001:Integrin alpha Chains; D015851:Interleukin-7; D008562:Membrane Glycoproteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C085725:integrin alpha7