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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.

Original publication

DOI

10.4049/jimmunol.1500686

Type

Journal article

Journal

J immunol

Publication Date

01/09/2016

Volume

197

Pages

1957 - 1967

Keywords

Animals, Gene Expression Regulation, Inflammation, Interleukin-7, Lymphangiogenesis, Lymphatic Vessels, Lymphotoxin alpha1, beta2 Heterotrimer, Mice, Salivary Glands, Signal Transduction, Tertiary Lymphoid Structures