title: TNFα-dependent development of lymphoid tissue in the absence of RORγt⁺ lymphoid tissue inducer cells.
abstract: Lymphoid tissue often forms within sites of chronic inflammation. Here we report that expression of the proinflammatory cytokine tumor necrosis factor α (TNFα) drives development of lymphoid tissue in the intestine. Formation of this ectopic lymphoid tissue was not dependent on the presence of canonical RORgt(+) lymphoid tissue-inducer (LTi) cells, because animals expressing increased levels of TNFα but lacking RORgt(+) LTi cells (TNF/Rorc(gt)(-/-) mice) developed lymphoid tissue in inflamed areas. Unexpectedly, such animals developed several lymph nodes (LNs) that were structurally and functionally similar to those of wild-type animals. TNFα production by F4/80(+) myeloid cells present within the anlagen was important for the activation of stromal cells during the late stages of embryogenesis and for the activation of an organogenic program that allowed the development of LNs. Our results show that lymphoid tissue organogenesis can occur in the absence of LTi cells and suggest that interactions between TNFα-expressing myeloid cells and stromal cells have an important role in secondary lymphoid organ formation.
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: G C
authors.initials: GC
authors.lastname: Furtado
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Pacer
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: G
authors.initials: G
authors.lastname: Bongers
authors.affiliation: IBR-MRC Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: C
authors.initials: C
authors.lastname: Bénézech
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: He
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Chen
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Berin
authors.affiliation: Alexander Fleming Biomedical Sciences Research Center, Vari, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Kollias
authors.affiliation: IBR-MRC Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Caamaño
authors.affiliation: Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Lira
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008221:Lymphoid Tissue / Q000196:embryology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D039481:CD11b Antigen; D051797:Inhibitor of Differentiation Protein 2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D014409:Tumor Necrosis Factor-alpha; C036763:monocyte-macrophage differentiation antigen