title: Hematopoietic LTβR deficiency results in skewed T cell cytokine profiles during a mucosal viral infection.
abstract: The lymphotoxin signaling pathway plays an important role in the homeostasis and function of peripheral and mucosal dendritic cells, and dendritic cell-intrinsic lymphotoxin β receptor expression is required for optimal responses to opportunistic intestinal bacteria. However, it is unknown whether dendritic cell-intrinsic lymphotoxin β receptor signaling is required for responses to intestinal viral infections. We explored this question by orally administrating murine rotavirus to chimeric mice that lack lymphotoxin β receptor signaling in the myeloid compartment but retain lymphoid tissues. We found that although clearance of rotavirus was unimpaired in the lymphotoxin β receptor(-/-) → wild-type chimeric mice compared with wild-type → wild-type chimeric mice, IFN-γ-producing CD8(+) and CD4(+) T cells were significantly increased in the small intestinal lamina propria of lymphotoxin β receptor(-/-) → wild-type chimeric mice. In contrast, IL-17-producing CD4(+) T cells were reduced in lymphotoxin β receptor(-/-) → wild-type chimeric mice in the steady state, and this reduction persisted after rotavirus inoculation. In spite of this altered cytokine profile in the small intestinal lamina propria of lymphotoxin β receptor(-/-) → wild-type chimeric mice, the local production of rotavirus-specific IgA was unperturbed. Collectively, our results demonstrate that lymphotoxin β receptor signaling in radio-sensitive myeloid cells regulates the balance of IFN-γ and IL-17 cytokine production within the small intestinal lamina propria; however, these perturbations do not affect mucosal antiviral IgA responses.
authors.affiliation: Department of Immunology, University of Toronto, Ontario, Canada.
authors.forename: Tian
authors.initials: T
authors.lastname: Sun
authors.affiliation: Department of Immunology, University of Toronto, Ontario, Canada.
authors.forename: Olga L
authors.initials: OL
authors.lastname: Rojas
authors.affiliation: Department of Immunology, University of Toronto, Ontario, Canada.
authors.forename: Conglei
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Immunology, University of Toronto, Ontario, Canada.
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.affiliation: Department of Immunology, University of Toronto, Ontario, Canada jen.gommerman@utoronto.ca.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gommerman
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology*; D053259:Lymphotoxin beta Receptor / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D007070:Immunoglobulin A; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor
keywords: dendritic cell; rotavirus; small intestine; tumor necrosis factor