Wu, Y., Huang, J. Y., Conlon, M. T., Shenoy, M. K., Chao, J. L., Chooi, M. Y., Koch, M. A., & Gerner, M. Y. (2024). Distal Immunization and Systemic Cytokines Establish a Transient Immune Alert State in the Intestine. The Journal of Immunology, 213(3), 373–383. https://doi.org/10.4049/jimmunol.2400209
Abstract:
Conventionally, immune responses are studied in the context of inflamed tissues and their corresponding draining lymph nodes (LNs). However, little is known about the effects of systemic inflammatory signals generated during local inflammation on distal tissues and nondraining LNs. Using a mouse model of cutaneous immunization, we found that systemic inflammatory stimuli triggered a rapid and selective distal response in the small intestine and the mesenteric LN (mesLN). This consisted of increased permeability of intestinal blood vessels and lymphatic drainage of bloodborne solutes into the mesLN, enhanced activation and migration of intestinal dendritic cells, as well as amplified T cell responses in the mesLNs to systemic but not orally derived Ags. Mechanistically, we found that the small intestine endothelial cells preferentially expressed molecules involved in TNF-α signaling and that TNF-α blockade markedly diminished distal intestinal responses to cutaneous immunization. Together, these findings reveal that the intestinal immune system is rapidly and selectively activated in response to inflammatory cues regardless of their origin, thus identifying an additional layer of defense and enhanced surveillance of a key barrier organ at constant risk of pathogen encounter.
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Funding Info:
This research / project is supported by the National Institute of Health - National Institute of Health Grant
Grant Reference no. : A173128
This research / project is supported by the Rita Allen Foundation - NA
Grant Reference no. : NA
This research / project is supported by the Pew Charitable Trusts - NA
Grant Reference no. : NA
This research / project is supported by the Fred Hutchinson Cancer Center - NA
Grant Reference no. : NA
Description:
This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Immunology following peer review. The version of record Wu, Y., Huang, J. Y., Conlon, M. T., Shenoy, M. K., Chao, J. L., Chooi, M. Y., Koch, M. A., & Gerner, M. Y. (2024). Distal Immunization and Systemic Cytokines Establish a Transient Immune Alert State in the Intestine. The Journal of Immunology, 213(3), 373–383. is available online at: https://doi.org/10.4049/jimmunol.2400209