Autoimmune diseases (AIDs), including systemic lupus erythematosus (SLE), anti-synthetase syndrome (ASS), systemic sclerosis (SSc), and multiple sclerosis (MS), are triggered by abnormal adaptive immunity and have various clinical manifestations. In these patients, immune intolerance to antigens leads to the formation of autoreactive T and B cells, which attack their own organs^1,2 (Fig. 1). Additionally, AIDs are associated with inadequate negative regulation of abnormal immune responses by regulatory T cells (Tregs) ³. AIDs affect approximately 10% of the global population and rank among the leading causes of disability and mortality. A substantial proportion of patients present with severe, complex, and rapidly progressive disease for which curative therapies are lacking, representing a long-standing clinical challenge ⁴. AID can be classified into systemic and organ-specific according to their cumulative range. Examples of systemic AIDs include SLE, SSc, Sjögren Syndrome (SS), and rheumatoid arthritis (RA). Common organ-specific AIDs include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), autoimmune encephalomyelitis (AE), and autoimmune cholangitis ⁵.

Immunosuppressants, including corticosteroids and disease-modifying anti-rheumatic drugs, are commonly used to treat AIDs. They suppress the immune system by inhibiting the inflammatory cascade, reducing disease severity, and slowing its progression; however, they do not cure the disease ⁶. Given the critical role of B cells in the development of AIDs, B cell depletion may be a potential cure. Monoclonal antibodies and antibody-drug conjugates targeting B cell surface antigens are also currently used in AID therapy but have shown limited efficacy ⁷.

Conventional autologous hematopoietic stem cell transplantation (ASCT) relies on high-dose chemotherapy ± total-body irradiation to eradicate aberrantly activated autoreactive T and B lymphocytes and force an immune-system “reset.” The reconstructed immune system may restore tolerance to autoantigens, thereby reducing or terminating autoimmune responses. ASCT may induce long-term remission or even functional cure in various refractory diseases. However, its substantial treatment-related toxicity—encompassing transplant-related mortality, severe infections, and disease relapse—coupled with rigorous patient-selection criteria, confines ASCT to a narrow, carefully chosen population ⁸. Chimeric antigen receptor T cells (CAR-T) were first used for the treatment of hematological malignancies. In vitro gene editing technology enables CAR-T cells to express chimeric antigen receptors (CAR).