Inflammation recapitulates the ontogeny of lymphoid stromal cells.
Stromal cells in lymphoid tissues regulate lymphocyte recruitment and survival through the expression of specific chemokines and cytokines. During inflammation, the same signals recruit lymphocytes to the site of injury; however, the "lymphoid" stromal (LS) cells producing these signals remain poorly characterized. We find that mouse inflammatory lesions and tumors develop gp38(+) LS cells, in recapitulation of the development of LS cells early during the ontogeny of lymphoid organs and the intestine, and express a set of genes that promotes the development of lymphocyte-permissive tissues. These gp38(+) LS cells are induced by a robust pathway that requires myeloid cells but not known Toll- or NOD-like receptors, the inflammasome, or adaptive immunity. Parabiosis and inducible genetic cell fate mapping experiments indicate that local precursors, presumably resident fibroblasts rather that circulating precursors, massively proliferate and give rise to LS cells during inflammation. Our results show that LS cells are both programmed during ontogeny and reinduced during inflammation.
Peduto
Lucie
L
Laboratory of Lymphoid Tissue Development, Institut Pasteur, Centre National de la Recherche Scientifique, Unité de Recherche Associée 1961, Paris, France.
Dulauroy
Sophie
S
Lochner
Matthias
M
Späth
Gerald F
GF
Morales
Miguel A
MA
Cumano
Ana
A
Eberl
Gérard
G
D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D007249:Inflammation / Q000196:embryology / Q000276:immunology* / Q000473:pathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000196:embryology / Q000276:immunology / Q000473:pathology; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000473:pathology; D008221:Lymphoid Tissue / Q000196:embryology / Q000276:immunology* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D008822:Mice, Transgenic; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000098853:Podoplanin
D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C490441:Pdpn protein, mouse; D000098853:Podoplanin