Research Topic

The Role of PPARgamma in Immune Homeostasis

About this Research Topic

PPAR (peroxisome proliferator-activated receptor) family members are among the most widely studied transcription factors. These nuclear receptor proteins exert transcription factor activities and influence multiple cellular events at the molecular level including cell differentiation and development, ...

PPAR (peroxisome proliferator-activated receptor) family members are among the most widely studied transcription factors. These nuclear receptor proteins exert transcription factor activities and influence multiple cellular events at the molecular level including cell differentiation and development, metabolism and carcinogenesis. This broad spectrum highlights that PPARs are key players of numerous physiological and pathological events. Amongst the PPAR family members, PPARgamma (known to exist in three variant forms) is of particular interest as it is broadly expressed in the mammalian body including all adipose tissue subtypes (white, brown, beige) and also in the intestine, kidneys, pancreas, muscles, placenta, spleen and thymus. As suggested by its expression pattern PPARgamma is indispensable for adipose tissue development, but has also multiple other, context-dependent functions.

PPARgamma expression has been reported in several cell types and tissues directly related to immune function (i.e. macrophages, thymocytes) or indirectly to immunological niches (i.e. bone marrow or thymic stroma). It is therefore not surprising that PPARgamma can influence immune status in both health and disease. Since PPARgamma expression and activity changes with age, this indicates that PPARgamma may be correlated with immune homeostasis. However, the effect of PPARgamma on immune homeostasis remains poorly understood and controversial. On one hand, PPARgamma activity is necessary for maintaining a permissive bone marrow niche to support hemopoietic stem cell maintenance. On the other hand, progenitor niches (such as the thymic stroma) may be negatively impacted by PPARgamma activity that drives aging-related adipose involution.

Immune homeostasis disequilibrium is linked with the development of certain diseases that are highly prevalent in aged patients, such as cancer. The role of PPARgamma in cancer development and metastasis formation has thus far been reported in a limited number of tissues. Lung cancer statistics increase unfavorably worldwide, putting lung cancer research at center stage. Of note, PPARgamma has a rather puzzling, enigmatic role in lung tumor formation and metastasis. Even though elevated PPARgamma activity delays the development of individual lung cancer cells, once a tumor mass has been established, increased PPARgamma activity actually facilitates metastasis of the tumor to other tissues.

Given the number and significance of PPARgamma-related physiological processes and diseases, it is not surprising that PPARgamma loss-of-function leads to the development of severe disorders with a predominantly metabolic phenotype. In the murine setting, placental dependence on PPARgamma necessitates the use of conditional knock-out animal models to study the role of PPARgamma in different tissues. In humans, spontaneous loss of PPARgamma function is a very rare disease causing a predominantly metabolic phenotype (FPLD3: familial partial lipodystrophy, type 3). Since metabolic alterations often shorten life expectancy, studies on immune aging become challenging, but should remain feasible at the molecular level.

This Research Topic aims to decipher the role of PPARgamma in immune homeostasis with a focus on hematopoietic homeostasis, immune micro-environments, carcinogenesis and inflammation. We welcome the submission of Review and Original Research Articles to this Research Topic to expand basic knowledge in the above fields.


Keywords: PPARgamma, Metabolism, Immune System, Aging, Tumor Formation


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15 December 2017 Manuscript

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Manuscripts can be submitted to this Research Topic via the following journals:

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Submission Deadlines

15 December 2017 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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