Macrophage Plasticity and Polarization in Liver Homeostasis ... : Hepatology (original) (raw)

NEW HORIZONS

1 Humanitas Clinical and Research Center, Rozzano, Italy

2 DiSCAFF, University of Piemonte Orientale A. Avogadro, Novara, Italy

3 Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Italy

4 BIOMETRA Department, University of Milan, Milan, Italy

Received 21 May 2013; accepted 13 September 2013.

Address reprint requests to: Alberto Mantovani, M.D., Humanitas Clinical and Research Center, via Manzoni 56, 20089 Rozzano, Milan, Italy. E-mail:[email protected]; fax: +39 02 82245101.

Potential conflict of interest: Dr. Mantovani and Dr. Sica received grants from Johnson & Johnson.

This work was supported by Associazione Italiana Ricerca sul Cancro (AIRC), Italy, Fondazione Cariplo, Italy, Ministero Università Ricerca (MIUR) e Salute, and by the European Commission (ERC project no.: 233417 HIIS; to A.M.).

A full reference list is available as Supporting Information. We apologize to colleagues who, because of space limitations, are only cited there.

Additional Supporting Information may be found in the online version of this article.

Abstract

Resident and recruited macrophages are key players in the homeostatic function of the liver and in its response to tissue damage. In response to environmental signals, macrophages undergo polarized activation to M1 or M2 or M2-like activation states. These are extremes of a spectrum in a universe of activation states. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of mononuclear phagocytes. Resident and recruited macrophages are a key component of diverse homeostatic and pathological responses of hepatic tissue. Polarized macrophages interact with hepatic progenitor cells, integrate metabolic adaptation, mediate responses to infectious agents, orchestrate fibrosis in a yin-yang interaction with hepatic stellate cells, and are a key component of tumor-promoting inflammation.

Conclusion:

A better understanding of macrophage diversity and plasticity in liver homeostasis and pathology may pave the way to innovative diagnostic and therapeutic approaches. (Hepatology 2014;59:2034–2042)