Bimodal Expansion of the Lymphatic Vessels Is Regulated by the Sequential Expression of IL-7 and Lymphotoxin α1β2 in Newly Formed Tertiary Lymphoid Structures.

Nayar S; Campos J; Chung MM; Navarro-Núñez L; Chachlani M; Steinthal N; Gardner DH; Rankin P; Cloake T; Caamaño JH; McGettrick HM; Watson SP; Luther S; Buckley CD; Barone F

doi:10.4049/jimmunol.1500686

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Bimodal Expansion of the Lymphatic Vessels Is Regulated by the Sequential Expression of IL-7 and Lymphotoxin α1β2 in Newly Formed Tertiary Lymphoid Structures.

Nayar S 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;
Campos J 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;
Chung MM 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;
Navarro-Núñez L Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
Chachlani M 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;
Steinthal N 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;
Gardner DH 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;
Rankin P 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;
Cloake T 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;
Caamaño JH Medical Research Council Centre for Immune Regulation, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom; and.
McGettrick HM 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;
Watson SP Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
Luther S Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
Buckley CD 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;
Barone F 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.

2016-07-31

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Journal of immunology (Baltimore, Md. : 1950). - 2016

Lymphotoxin alpha1, beta2 Heterotrimer

English 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.

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