title: Maturation of lymph node fibroblastic reticular cells from myofibroblastic precursors is critical for antiviral immunity.
abstract: The stromal scaffold of the lymph node (LN) paracortex is built by fibroblastic reticular cells (FRCs). Conditional ablation of lymphotoxin-β receptor (LTβR) expression in LN FRCs and their mesenchymal progenitors in developing LNs revealed that LTβR-signaling in these cells was not essential for the formation of LNs. Although T cell zone reticular cells had lost podoplanin expression, they still formed a functional conduit system and showed enhanced expression of myofibroblastic markers. However, essential immune functions of FRCs, including homeostatic chemokine and interleukin-7 expression, were impaired. These changes in T cell zone reticular cell function were associated with increased susceptibility to viral infection. Thus, myofibroblasic FRC precursors are able to generate the basic T cell zone infrastructure, whereas LTβR-dependent maturation of FRCs guarantees full immunocompetence and hence optimal LN function during infection.
authors.affiliation: Institute of Immunobiology, Kantonal Hospital St. Gallen, 9007 St. Gallen, Switzerland.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chai
authors.forename: Lucas
authors.initials: L
authors.lastname: Onder
authors.forename: Elke
authors.initials: E
authors.lastname: Scandella
authors.forename: Cristina
authors.initials: C
authors.lastname: Gil-Cruz
authors.forename: Christian
authors.initials: C
authors.lastname: Perez-Shibayama
authors.forename: Jovana
authors.initials: J
authors.lastname: Cupovic
authors.forename: Renzo
authors.initials: R
authors.lastname: Danuser
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.forename: Sanjiv A
authors.initials: SA
authors.lastname: Luther
authors.forename: Volker
authors.initials: V
authors.lastname: Thiel
authors.forename: Thomas
authors.initials: T
authors.lastname: Rülicke
authors.forename: Jens V
authors.initials: JV
authors.lastname: Stein
authors.forename: Thomas
authors.initials: T
authors.lastname: Hehlgans
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D018352:Coronavirus Infections / Q000276:immunology*; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D015851:Interleukin-7 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D053259:Lymphotoxin beta Receptor / Q000378:metabolism; D053308:Lymphotoxin-beta / Q000096:biosynthesis / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D006517:Murine hepatitis virus / Q000276:immunology; D058628:Myofibroblasts / Q000166:cytology / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D000098853:Podoplanin
chemical_list: D015851:Interleukin-7; D053259:Lymphotoxin beta Receptor; D053308:Lymphotoxin-beta; D008562:Membrane Glycoproteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin