title: Bimodal Expansion of the Lymphatic Vessels Is Regulated by the Sequential Expression of IL-7 and Lymphotoxin α1β2 in Newly Formed Tertiary Lymphoid Structures.
abstract: Lymphangiogenesis associated with tertiary lymphoid structure (TLS) has been reported in numerous studies. However, the kinetics and dynamic changes occurring to the lymphatic vascular network during TLS development have not been studied. Using a viral-induced, resolving model of TLS formation in the salivary glands of adult mice we demonstrate that the expansion of the lymphatic vascular network is tightly regulated. Lymphatic vessel expansion occurs in two distinct phases. The first wave of expansion is dependent on IL-7. The second phase, responsible for leukocyte exit from the glands, is regulated by lymphotoxin (LT)βR signaling. These findings, while highlighting the tight regulation of the lymphatic response to inflammation, suggest that targeting the LTα1β2/LTβR pathway in TLS-associated pathologies might impair a natural proresolving mechanism for lymphocyte exit from the tissues and account for the failure of therapeutic strategies that target these molecules in diseases such as rheumatoid arthritis.
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: Saba
authors.initials: S
authors.lastname: Nayar
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: Joana
authors.initials: J
authors.lastname: Campos
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: Ming May
authors.initials: MM
authors.lastname: Chung
authors.affiliation: Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
authors.forename: Leyre
authors.initials: L
authors.lastname: Navarro-Núñez
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: Menka
authors.identifier: 0000-0001-5628-3079
authors.initials: M
authors.lastname: Chachlani
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: Nathalie
authors.identifier: 0000-0003-0422-950X
authors.initials: N
authors.lastname: Steinthal
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: David H
authors.initials: DH
authors.lastname: Gardner
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: Philip
authors.identifier: 0000-0003-1633-7313
authors.initials: P
authors.lastname: Rankin
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: Thomas
authors.initials: T
authors.lastname: Cloake
authors.affiliation: Medical Research Council Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom; and.
authors.forename: Jorge H
authors.identifier: 0000-0003-3530-7056
authors.initials: JH
authors.lastname: Caamaño
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: Helen M
authors.identifier: 0000-0002-5950-8840
authors.initials: HM
authors.lastname: McGettrick
authors.affiliation: Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
authors.forename: Steve P
authors.identifier: 0000-0002-7846-7423
authors.initials: SP
authors.lastname: Watson
authors.affiliation: Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
authors.forename: Sanjiv
authors.identifier: 0000-0002-8758-957X
authors.initials: S
authors.lastname: Luther
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom;
authors.forename: Christopher D
authors.identifier: 0000-0001-6924-6402
authors.initials: CD
authors.lastname: Buckley
authors.affiliation: Rheumatology Research Group, Centre for Translational Inflammation Research, Institute of Inflammation and Ageing, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham B15 2WD, United Kingdom; f.barone@bham.ac.uk.
authors.forename: Francesca
authors.identifier: 0000-0002-5287-9614
authors.initials: F
authors.lastname: Barone
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D007249:Inflammation; D015851:Interleukin-7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000276:immunology* / Q000378:metabolism; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D012469:Salivary Glands / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D000072717:Tertiary Lymphoid Structures / Q000276:immunology* / Q000473:pathology
chemical_list: D015851:Interleukin-7; D053361:Lymphotoxin alpha1, beta2 Heterotrimer