Thymosin α1: An endogenous regulator of inflammation, immunity, and tolerance

Luigina Romani, Francesco Bistoni, Claudia Montagnoli, Roberta Gaziano, Silvia Bozza, Pierluigi Bonifazi, Teresa Zelante, Silvia Moretti, Guido Rasi, Enrico Garaci, Paolo Puccetti

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Thymosin α1 (Tα1), first described and characterized by Allan Goldstein in 1972, is used worldwide for the treatment of some immunodeficiencies, malignancies, and infections. Although Tα1 has shown a variety of effects on cells and pathways of the immune system, its central role in modulating dendritic cell (DC) function has only recently been appreciated. As DCs have the ability to sense infection and tissue stress and to translate collectively this information into an appropriate immune response, an action on DCs would predict a central role for Tα1 in inducing different forms of immunity and tolerance. Recent results have shown that Tα1: (a) primed DCs for antifungal Th1 resistance through Toll-like receptor (TLR)/MyD88-dependent signaling and this translated in vivo in protection against aspergillosis; (b) activated plasmacytoid DCs (pDC) via the TLR9/MyD88-dependent viral recognition, thus leading to the activation of interferon regulatory factor 7 and the promotion of the IFN-α/IFN-γ-dependent effector pathway, which resulted in vivo in protection against primary murine cytomegalovirus infection; (c) induced indoleamine 2,3-dioxygenase activity in DCs, thus affecting tolerization toward self as well as microbial non-self-antigens, and this resulted in vivo in transplantation tolerance and protection from inflammatory allergy. Tα1 is produced in vivo by cleavage of prothymosin α in diverse mammalian tissues. Our data qualify Tα1 as an endogenous regulator of immune homeostasis and suggest that instructive immunotherapy with Tα1, via DCs and tryptophan catabolism, could be at work to control inflammation, immunity, and tolerance in a variety of clinical settings.

Original languageEnglish
Title of host publicationAnnals of the New York Academy of Sciences
Pages326-338
Number of pages13
Volume1112
DOIs
Publication statusPublished - Sep 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1112
ISSN (Print)00778923
ISSN (Electronic)17496632

Keywords

  • Dendritic cells
  • Immunity and tolerance
  • Regulatory T cells
  • Thymosin
  • Toll-like receptors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Romani, L., Bistoni, F., Montagnoli, C., Gaziano, R., Bozza, S., Bonifazi, P., Zelante, T., Moretti, S., Rasi, G., Garaci, E., & Puccetti, P. (2007). Thymosin α1: An endogenous regulator of inflammation, immunity, and tolerance. In Annals of the New York Academy of Sciences (Vol. 1112, pp. 326-338). (Annals of the New York Academy of Sciences; Vol. 1112). https://doi.org/10.1196/annals.1415.002