Open AccessA Complement–IL-4 Regulatory Circuit Controls Liver Regeneration
Author(s) -
Robert A. DeAngelis,
Maciej M. Markiewski,
Ioannis Kourtzelis,
Stavros Rafail,
Maria Syriga,
Adam Sandor,
Mano R. Maurya,
Shakti Gupta,
Shankar Subramaniam,
John D. Lambris
Publication year - 2011
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.1101925
Subject(s) - liver regeneration , regeneration (biology) , complement system , biology , microbiology and biotechnology , secretion , parenchyma , immunology , complement (music) , classical complement pathway , alternative complement pathway , antibody , endocrinology , biochemistry , phenotype , gene , complementation , botany
The involvement of IL-4 in liver regeneration has not yet been recognized. In this article, we show that IL-4, produced by NKT cells that accumulate in regenerating livers after partial hepatectomy, contributes to this process by regulating the activation of complement after liver resection in mice. The mechanism of this regulation was associated with the maintenance of an appropriate level of IgM in mouse blood, because IgM deposited in liver parenchyma most likely initiated complement activation during liver regeneration. By controlling complement activation, IL-4 regulated the induction of IL-6, thereby influencing a key pathway involved in regenerating liver cell proliferation and survival. Furthermore, the secretion of IL-4 was controlled by complement through the recruitment of NKT cells to regenerating livers. Our study thus reveals the existence of a regulatory feedback mechanism involving complement and IL-4 that controls liver regeneration.
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