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Induction of antigen-specific tolerance by nanobody-antigen adducts that target class-II major histocompatibility complexes.
Pishesha, Novalia; Harmand, Thibault; Smeding, Liyan Y; Ma, Weiyi; Ludwig, Leif S; Janssen, Robine; Islam, Ashraful; Xie, Yushu J; Fang, Tao; McCaul, Nicholas; Pinney, William; Sugito, Harun R; Rossotti, Martin A; Gonzalez-Sapienza, Gualberto; Ploegh, Hidde L.
Afiliação
  • Pishesha N; Society of Fellows, Harvard University, Cambridge, MA, USA. novalia.pishesha@childrens.harvard.edu.
  • Harmand T; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA. novalia.pishesha@childrens.harvard.edu.
  • Smeding LY; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. novalia.pishesha@childrens.harvard.edu.
  • Ma W; Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA. novalia.pishesha@childrens.harvard.edu.
  • Ludwig LS; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Janssen R; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Islam A; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Xie YJ; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Fang T; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • McCaul N; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Pinney W; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
  • Sugito HR; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Rossotti MA; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Gonzalez-Sapienza G; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Ploegh HL; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
Nat Biomed Eng ; 5(11): 1389-1401, 2021 11.
Article em En | MEDLINE | ID: mdl-34127819
The association of autoimmune diseases with particular allellic products of the class-II major histocompatibility complex (MHCII) region implicates the presentation of the offending self-antigens to T cells. Because antigen-presenting cells are tolerogenic when they encounter an antigen under non-inflammatory conditions, the manipulation of antigen presentation may induce antigen-specific tolerance. Here, we show that, in mouse models of experimental autoimmune encephalomyelitis, type 1 diabetes and rheumatoid arthritis, the systemic administration of a single dose of nanobodies that recognize MHCII molecules and conjugated to the relevant self-antigen under non-inflammatory conditions confers long-lasting protection against these diseases. Moreover, co-administration of a nanobody-antigen adduct and the glucocorticoid dexamethasone, conjugated to the nanobody via a cleavable linker, halted the progression of established experimental autoimmune encephalomyelitis in symptomatic mice and alleviated their symptoms. This approach may represent a means of treating autoimmune conditions.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encefalomielite Autoimune Experimental / Tolerância Imunológica Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encefalomielite Autoimune Experimental / Tolerância Imunológica Limite: Animals Idioma: En Ano de publicação: 2021 Tipo de documento: Article