title: IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population.
abstract: Patients who survive sepsis can develop long-term immune dysfunction, with expansion of the regulatory T (Treg) cell population. However, how Treg cells proliferate in these patients is not clear. Here we show that IL-33 has a major function in the induction of this immunosuppression. Mice deficient in ST2 (IL-33R) develop attenuated immunosuppression in cases that survive sepsis, whereas treatment of naive wild-type mice with IL-33 induces immunosuppression. IL-33, released during tissue injury in sepsis, activates type 2 innate lymphoid cells, which promote polarization of M2 macrophages, thereby enhancing expansion of the Treg cell population via IL-10. Moreover, sepsis-surviving patients have more Treg cells, IL-33 and IL-10 in their peripheral blood. Our study suggests that targeting IL-33 may be an effective treatment for sepsis-induced immunosuppression.
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Nascimento
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Paulo H
authors.initials: PH
authors.lastname: Melo
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Annie R
authors.initials: AR
authors.lastname: Piñeros
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Raphael G
authors.initials: RG
authors.lastname: Ferreira
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: David F
authors.initials: DF
authors.lastname: Colón
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Paula B
authors.initials: PB
authors.lastname: Donate
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Fernanda V
authors.initials: FV
authors.lastname: Castanheira
authors.affiliation: Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Gozzi
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Paula G
authors.initials: PG
authors.lastname: Czaikoski
authors.affiliation: Department of Immunology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.
authors.forename: Wanda
authors.initials: W
authors.lastname: Niedbala
authors.affiliation: Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Marcos C
authors.initials: MC
authors.lastname: Borges
authors.affiliation: Departments of Cell Biology and Microbial Pathogenesis, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Dario S
authors.identifier: 0000-0002-7856-7512
authors.initials: DS
authors.lastname: Zamboni
authors.affiliation: Department of Immunology, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK.|School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215006, China.
authors.forename: Foo Y
authors.initials: FY
authors.lastname: Liew
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Departments of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto 14049-900, Brazil.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Alves-Filho
mesh_terms: D000368:Aged; D000818:Animals; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33 / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D016753:Interleukin-10