2. Academic Validation
  3. DC-CD4 bispecific tolerogenic nanovesicles induce antigen-specific regulatory T cells and ameliorate collagen-induced arthritis in mice

DC-CD4 bispecific tolerogenic nanovesicles induce antigen-specific regulatory T cells and ameliorate collagen-induced arthritis in mice

  • Nat Commun. 2026 Mar 19;17(1):4170. doi: 10.1038/s41467-026-70898-y.
Lei Zhao # 1 2,  Zhongqiang Gao # 3,  Ze Yuan # 4,  Xiaodie Yang 5,  Duxin Li 1,  Qian Ren 6,  Yunli Yu 7,  Jie Pan 8,  Yiran Zheng 9,  Xinyun Zhang 10
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Soochow Medical College of Soochow University, Biomedical Basic Research Center (BBRC) of Jiangsu Province, Soochow University, Suzhou, Jiangsu, P. R. China.
  • 2 Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
  • 3 Department of Pharmacy, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
  • 4 School of Life Sciences and Health Engineering, Jiangnan University, Wuxi, Jiangsu, P. R. China.
  • 5 Department of Pharmacy, The Fourth Affiliated Hospital of Soochow University, Suzhou Dushu Lake Hospital, Medical Center of Soochow University, Suzhou, Jiangsu, P. R. China.
  • 6 Laboratory Animal Center of Suzhou Medical College, Soochow University, Suzhou, Jiangsu, P. R. China.
  • 7 Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China. [email protected].
  • 8 Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China. [email protected].
  • 9 College of Pharmaceutical Sciences, Soochow Medical College of Soochow University, Biomedical Basic Research Center (BBRC) of Jiangsu Province, Soochow University, Suzhou, Jiangsu, P. R. China. [email protected].
  • 10 Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China. [email protected].
  • # Contributed equally.
PMID: 41851116 DOI: 10.1038/s41467-026-70898-y
Abstract

Inducing antigen-specific regulatory T (Treg) cells is a promising strategy for treating autoimmune diseases (AID). Here, we present dendritic cells-CD4⁺ T cells (DC-CD4) bispecific tolerogenic nanovesicles (NV) co-loaded with an antigenic peptide and rapamycin. We show that these NVs bring DCs and CD4⁺ T cells into close spatial proximity through CTLA4-CD80/86 and anti-CD4 (aCD4)-CD4 interactions, thereby promoting antigen-specific Treg cell generation. In a collagen-induced arthritis mouse model, the bispecific NVs display enhanced lymph node (LN) tropism and increase antigen-specific Treg cells in LNs and spleen, when administered in both therapeutic and prophylactic settings, resulting in robust efficacy against CIA. Furthermore, arthritogenic cell transfer and adoptive transfer of Treg cells into Treg-ablated mice confirm the pivotal role of bispecific NV-induced antigen-specific Treg cells in mediating the anti-inflammatory efficacy. Collectively, our data support DC-CD4 bispecific tolerogenic NVs as a platform to induce antigen-specific Treg cells for precise immune tolerance in AIDs.

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