Intranasally Induced Immunological Tolerance Is Determined by Characteristics of the Draining Lymph Nodes: Studies with OVA and Human Cartilage gp-39

TLDR

Mucosal tolerance prevents harmful inflammatory responses to inhaled or ingested antigens, and the nasal mucosa is a highly efficient site for inducing such tolerance, offering a potential strategy for antigen‑specific autoimmune therapy. In a mouse model using OVA and human cartilage gp‑39, the authors demonstrate that superficial cervical and internal jugular lymph nodes draining the nasal mucosa are essential for tolerance induction. Ablation of these lymph nodes abolishes tolerance, which can be reinstated only by transplanting superficial cervical nodes, underscoring that nasal‑draining lymph nodes provide a unique microenvironment that promotes immunological tolerance.

Abstract

Mucosal tolerance is a naturally occurring immunological phenomenon that prevents harmful inflammatory responses to ingested or inhaled environmental, predominantly nondangerous, Ags. The nasal mucosa is an extremely efficient compartment in the induction of immunological tolerance which can be exploited in Ag-specific treatment of autoimmune disease. With the use of a model Ag (OVA) and an Ag implicated in the autoimmune disease rheumatoid arthritis (human cartilage gp-39), we here show in a mouse model that the superficial cervical and internal jugular lymph nodes that drain the nasal mucosa are instrumental in the induction of tolerance. Removal of these lymph nodes abrogates tolerance induction, which can be restored by transplantation of superficial cervical lymph nodes, but not of peripheral lymph nodes. The results indicate that lymph nodes that directly drain the nasal mucosa constitute a unique microenvironment which favors the induction of immunological tolerance.