Targeting TLR4 during vaccination boosts MAdCAM-1⁺ lymphoid stromal cell activation and promotes the aged germinal center response.

ABSTRACT: The failure to generate enduring humoral immunity after vaccination is a hallmark of advancing age. This can be attributed to a reduction in the germinal center (GC) response, which generates long-lived antibody-secreting cells that protect against (re)infection. Despite intensive investigation, the primary cellular defect underlying impaired GCs in aging has not been identified. Here, we used heterochronic parabiosis to demonstrate that GC formation was dictated by the age of the lymph node (LN) microenvironment rather than the age of the immune cells. Lymphoid stromal cells are a key determinant of the LN microenvironment and are also an essential component underpinning GC structure and function. Using mouse models, we demonstrated that mucosal adressin cell adhesion molecule-1 (MAdCAM-1

SUBMITTER: Denton AE 

PROVIDER: S-EPMC7612953 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature