Macrophage-specific PPARγ controls alternative activation and improves insulin resistance

Odegaard, Justin I.; Ricardo-González, Roberto R.; Goforth, Matthew H.; Morel, Christine R.; Subramanian, Vidya; Mukundan, Lata; Eagle, Alex Red; Vats, Divya; Brombacher, Frank; Ferrante, Anthony W.; Chawla, Ajay

doi:10.1038/nature05894

Cited by 1,857 publications

(1,875 citation statements)

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“…In vivo counterparts of M2 macrophage polarization have been observed in tissue remodelling during ontogenesis [28], chronic inflammation [29][30][31][32][33][34][35][36][37][38][39][40][41][42], cancer [9,12,16,17], bacterial [43][44][45][46][47][48][49] and parasitic [50][51][52][53] infections. Evidence has also accumulated that polarized macrophages are more than mere spectators of immunopathology [35][36][37][38][39][40][41][50][51][52].…”

Section: Activation and Adaptive Responses Of Macrophagesmentioning

confidence: 99%

“…Evidence has also accumulated that polarized macrophages are more than mere spectators of immunopathology [35][36][37][38][39][40][41][50][51][52].…”

Section: Activation and Adaptive Responses Of Macrophagesmentioning

confidence: 99%

“…For instance, do MDSC retain an immature phenotype in tumour tissues or do they differentiate into tumourassociated macrophages [9][10][11] [9,12,16,17], bacterial [43][44][45][46][47][48][49] and parasitic [50][51][52][53] infections. Evidence has also accumulated that polarized macrophages are more than mere spectators of immunopathology [35][36][37][38][39][40][41][50][51][52].…”

Section: Introductionmentioning

confidence: 99%

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From phagocyte diversity and activation to probiotics: Back to Metchnikoff

Mantovani

2008

Eur J Immunol

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In this issue of the European Journal of Immunology, Siamon Gordon gives a detailed account of Metchnikoff's life and his achievements (Eur. J. Immunol. 2008. 38: 3257-3264). Looking back at the roots of innate immunity stimulates reflections on open issues in the field. Here, I give a personal view of some of these issues, including myeloid-derived suppressor cells, macrophage polarization and adaptive responses of mononuclear phagocytes. Key words: Macrophage activation Á Macrophages Á M1/M2 polarization Á Probiotics See accompanying article by Gordon IntroductionIn his scholarly review [1], Siamon Gordon tracks the roots of innate immunity to Elie Metchnikoff. The essay provides a fascinating insight into Metchnikoff's scientific life and how he tackled fundamental issues in science, some of which remain with us to this day. The perspective offered by a major player in the very same field of phagocytes and innate immunity [2,3] adds flavour and fascination to this article not necessarily present in other accounts [4]. Such a reflection on a central part of modern immunology stimulates consideration of remaining open issues and there follows a personal view of some of these.Phagocyte heterogeneity: From microphage-macrophage dichotomy to myeloid-derived suppressor cellsThe fundamental distinction between polymorphonuclear leukocytes (microphages) and mononuclear phagocytes (macrophages) was a major first step in the dissection of phagocyte heterogeneity and lineage differentiation. The identification of myeloid-derived suppressor cells (MDSC) [5][6][7] raises the questions whether the classic sharp distinction between the myeloid and the monocyte-macrophage differentiation and activation pathways is appropriate. In contrast to long-held views, neutrophils express specific transcriptional programmes in response to environmental signals [8]. MDSC include immature myeloid precursors that can further differentiate, and play a key role in the suppression of adaptive immunity in diverse pathological conditions ranging from cancer to chronic infections [5][6][7]. Are we dealing with a blurring of a classic distinction or with a well-defined third phagocyte population? Using current identification and separation criteria (e.g. Gr1, CD11b, F4/80) MDSC in the blood and lymphoid organs are a mixed population, which includes myeloid cells at different stages of differentiation and mononuclear phagocytes. Thus, the definition of MDSC remains an operational one rather than that of a cell type, a reality that is frequently neglected. The issue of lineage of the actual effectors of MDSC-mediated suppression is even more relevant when their recruitment and activation in non-lymphoid tissues is considered. For instance, do MDSC retain an immature phenotype in tumour tissues or do they differentiate into tumourassociated macrophages [9][10][11] [9,12,16,17], bacterial [43][44][45][46][47][48][49] and parasitic [50][51][52][53] infections. Evidence has also accumulated that polarized macrophages are more than mere spectators of i...

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Section: Activation and Adaptive Responses Of Macrophagesmentioning

confidence: 99%

“…Evidence has also accumulated that polarized macrophages are more than mere spectators of immunopathology [35][36][37][38][39][40][41][50][51][52].…”

Section: Activation and Adaptive Responses Of Macrophagesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

From phagocyte diversity and activation to probiotics: Back to Metchnikoff

Mantovani

2008

Eur J Immunol

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“…Specifically, depletion of ILC2 elevated weight gain whereas treating obese mice with IL-25, thereby driving ILC2 responses, induced weight loss (Hams et al 2013). It is possible that ILC2 production of IL-13 enhances AAM polarization in adipose tissue and thus serves to protect from metabolic dysregulation and obesity (Odegaard et al 2007). …”

Section: Ilc2 Interactions With Innate Cellsmentioning

confidence: 99%

Innate Lymphoid Cells in Type 2 Immune Responses

Mirchandani

Salmond

2014

Arch. Immunol. Ther. Exp.

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In recent years, several distinct innate lymphoid cell populations (ILC) have been characterized in mice and humans. Group 2 ILC function as a rapid responder population in type 2 immune responses. Thus, a wealth of data has implicated an important role for ILC2 in immunity to parasitic infection and in immune pathology in inflammatory and allergic responses. In this review, we describe recent progress in our understanding of the development and ontogeny of ILC2 populations and the mechanisms by which these cells function in a variety of infection and disease settings. Finally, we emphasize recent findings indicating functional interactions between these innate cells and their adaptive CD4 ? Th2 cell counterparts.

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“…Dès 1998, Jiang et al [36] évoquaient l'hypothèse selon laquelle PPAR inhibait l'expression de protéines impliquées dans l'inflammation (comme l'IL-1 , l'IL-6, l'IL-8, le TNF ou la métalloprotéase 9). Plus récemment, Chawla et al [37] ont démontré que les agonistes de PPAR ont des effets antiinflammatoires indépendants de ce facteur de transcription. Même si le rôle précis de PPAR dans l'inflammation reste encore à élucider, il est indubitable que ce facteur de transcription a une place centrale dans le métabolisme lipidique et l'activation du macrophage via la régulation du récepteur scavenger CD36, la capture des LDL (low density lipoproteins) oxydées et sa capacité intrinsèque de se lier à des acides gras poly-insaturés ou oxydés [38].…”

Section: Métabolisme Des Lipidesunclassified