Targeting Lymphoid Tissues to Promote Immune Tolerance

The enormous research progress in autoimmune disorders makes the establishment of long‐term clinical tolerance to autoantigens an accessible goal. This strategy endows lymphoid tissues with the tolerogenic ability to induce an unresponsive state toward autoantigens. Lymphoid tissues, as the crossroads, play integral roles in initiating immune activation and immunoregulation. Enormous efforts have driven the exploration of targeting delivery of tolerogenic agents to lymphoid tissues to reverse autoimmune disorders. Herein, the development of various tolerogenic therapies for autoimmune diseases are reviewed, the mechanisms of action from various lymphoid tissues to appropriate cell types by different administration routes are highlighted, and examples of lymphoid tissue‐targeting strategies to improve tolerogenic therapy potency are discussed. First lymph nodes‐targeting strategies for tolerance induction after interstitial or intra‐lymph node (i.LN) injection are summarized, then liver and spleen‐mediated tolerance after intravenous administration are described, and finally oral tolerance‐based therapies are discussed. It is envisioned that tolerogenic therapy will emerge as a novel treatment for autoimmune diseases.