Type 1 conventional dendritic cells (cDC1s) are unique in their efferocytosis¹ and cross-presenting abilities², resulting in antigen (Ag)-specific T cell immunity³ or tolerance^4-8. However, the mechanisms underlying cDC1 tolerogenic function remain largely unknown. Here, we show that the erythropoietin receptor (EpoR) acts as a critical switch that determines the tolerogenic function of cDC1s and the threshold of Ag-specific T cell responses. In total lymphoid (TLI)-induced allograft tolerance^9,10, cDC1s upregulate EpoR expression, and conditional knockout of EpoR in cDC1s diminishes Ag-specific FOXP3⁺ T_reg induction and expansion, resulting in allograft rejection. Mechanistically, EpoR promotes efferocytosis-induced tolerogenic maturation^7,11 of splenic cDC1s towards late-stage CCR7⁺ cDC1s characterized by elevated integrin β8 gene¹² (Itgb8) expression, and conditional knockout of Itgb8 in cDC1s impairs TLI/ATS-induced tolerance. Migratory cDC1s in peripheral lymph nodes (pLNs) preferentially express EpoR and their FOXP3⁺ T_reg inducing capacity is enhanced by EPO. Reciprocally, loss of EpoR enables immunogenic maturation of both pLN migratory and splenic CCR7⁺ cDC1s by upregulating genes involved in MHC class II- and class I-mediated Ag presentation, cross-presentation, and costimulation. EpoR deficiency in cDC1s reduces tumor growth by enhancing anti‑tumor T‑cell immunity, particularly increasing the generation of precursor exhausted tumor Ag‑specific CD8⁺ T cells (T_pex)¹³ in tumor draining LNs and supporting their maintenance within tumors, while concurrently reducing intratumoral T_regs. Targeting EpoR on cDC1s to induce or inhibit T cell immune tolerance could pave the way for treating a variety of diseases. (Nature volume 650, pages 470–480 (2026) https://www.nature.com/articles/s41586-025-09824-z)