DUSP3 Genetic Deletion Confers M2-like Macrophage–Dependent Tolerance to Septic Shock | Zendy

Pratibha Singh | Zendy; Lien Dejager | Zendy; Mathieu Amand | Zendy; Emilie Théâtre | Zendy; Maud Vandereyken | Zendy; Tinatin Zurashvili | Zendy; Maneesh Singh | Zendy; Matthias Mack | Zendy; Steven Timmermans | Zendy; Lucia Musumeci | Zendy; Emmanuel Dejardin | Zendy; Tomas Mustelin | Zendy; Jo A. Van Ginderachter | Zendy; Michel Moutschen | Zendy; Cécile Oury | Zendy; Claude Libert | Zendy; Souad Rahmouni | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

DUSP3 Genetic Deletion Confers M2-like Macrophage–Dependent Tolerance to Septic Shock

Author(s) -

Pratibha Singh,

Lien Dejager,

Mathieu Amand,

Emilie Théâtre,

Maud Vandereyken,

Tinatin Zurashvili,

Maneesh Singh,

Matthias Mack,

Steven Timmermans,

Lucia Musumeci,

Emmanuel Dejardin,

Tomas Mustelin,

Jo A. Van Ginderachter,

Michel Moutschen,

Cécile Oury,

Claude Libert,

Souad Rahmouni

Publication year - 2015

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.1402431

Subject(s) - septic shock , macrophage , innate immune system , adoptive cell transfer , sepsis , macrophage polarization , ligation , immune system , biology , immunology , regulator , microbiology and biotechnology , secretion , t cell , endocrinology , in vitro , gene , biochemistry

DUSP3 is a small dual-specificity protein phosphatase with an unknown physiological function. We report that DUSP3 is strongly expressed in human and mouse monocytes and macrophages, and that its deficiency in mice promotes tolerance to LPS-induced endotoxin shock and to polymicrobial septic shock after cecal ligation and puncture. By using adoptive transfer experiments, we demonstrate that resistance to endotoxin is macrophage dependent and transferable, and that this protection is associated with a striking increase of M2-like macrophages in DUSP3(-/-) mice in both the LPS and cecal ligation and puncture models. We show that the altered response of DUSP3(-/-) mice to sepsis is reflected in decreased TNF production and impaired ERK1/2 activation. Our results demonstrate that DUSP3 plays a key and nonredundant role as a regulator of innate immune responses by mechanisms involving the control of ERK1/2 activation, TNF secretion, and macrophage polarization.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research