Abstract
Accumulating evidence indicates that the endocrine and immune systems engage in complex cross-talks in which a prominent role is played by thyroid hormones (THs). The increase of resident vs. monocyte recruited macrophages was shown to be an important effector of the TH 3,3′,5′-Triiodo-L-thyronine (T3)-induced protection against inflammation and a key role of T3 in inhibiting the differentiation of peripheral monocytes into macrophages was observed. Herein, we report on the role of T3 as a modulator of microglia, the specialized macrophages of the central nervous system (CNS). Mounting evidence supports a role of microglia and macrophages in the growth and invasion of malignant glioma. In this respect, we unveil the putative involvement of T3 in the microglia/glioma cell communication. Since THs are known to cross the blood-brain barrier, we suggest that T3 not only exerts a direct modulation of brain cancer cell itself but also indirectly promotes glioma growth through a modulation of microglia. Our observations expand available information on the role of TH system in glioma and its microenvironment and highlight the endocrine modulation of microglia as an important target for future therapeutic development of glioma treatments.
Highlights
The specialized macrophages of the central nervous system (CNS), namely microglia, constitute 5–20% of total glial cells (Ransohoff and Perry, 2009; Kettenmann et al, 2011; Saijo and Glass, 2011)
From a mechanistic point of view, we suggest that signal transducers and activators of transcription 3 (STAT3) activation and the release of CXCL9/10 are suitable candidates to answer the question of how microglia supports glioma growth
With respect to CNS pathological remodeling induced by dysregulation of plasmatic levels of thyroid hormones (THs), the characterization of the physiologic factors that regulate the establishment of the microglial/glioma network is challenging
Summary
The specialized macrophages of the central nervous system (CNS), namely microglia, constitute 5–20% of total glial cells (Ransohoff and Perry, 2009; Kettenmann et al, 2011; Saijo and Glass, 2011). Inflammatory insults, result in the rapid recruitment of blood-borne precursors to the respective tissue macrophage compartment (Yona and Jung, 2010) In this line, our data suggest that T3 contributes to limit inflammation by promoting the proliferation of peritoneal macrophages in situ, while inhibiting the potentially damaging cell recruitment from monocyte cell pools, in a context not fully explained by the ‘‘classically activated’’/‘‘alternatively activated’’ framework (Perrotta et al, 2014). It has been recently shown that hypothyroidism prominently reduces the processes of microglia in the hippocampus of diabetic rats (Nam et al, 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
