Related Experiment Video

Updated: May 19, 2026

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
07:12

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

Published on: April 16, 2015

TGFβ signalling plays an important role in IL4-induced alternative activation of microglia

Xiaolai Zhou1, Björn Spittau, Kerstin Krieglstein

  • 1Institute for Anatomy and Cell Biology, Department of Molecular Embryology, Albert-Ludwigs-University Freiburg, Albertstraße 17, Freiburg 79104, Germany.

Journal of Neuroinflammation
|September 6, 2012
PubMed
Abstract

Insights

Transforming growth factor beta (TGFβ) enhances interleukin-4 (IL4)-induced alternative activation of microglia, revealing its crucial role in neuroinflammation and immune regulation.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia, the central nervous system's immune cells, are implicated in neurodegenerative diseases.
  • Microglia exhibit classical (M1) and alternative (M2) activation states, similar to peripheral macrophages.
  • Transforming growth factor beta (TGFβ) is a key anti-inflammatory cytokine, primarily studied for inhibiting M1 activation, with its role in M2 activation unexplored.

Purpose of the Study:

  • To investigate the role of TGFβ in interleukin-4 (IL4)-induced alternative activation of microglia.
  • To elucidate the signaling pathways involved in TGFβ-mediated modulation of microglial alternative activation.

Main Methods:

  • Utilized BV2 and primary mouse microglia treated with IL4, TGFβ, or both.
  • Assessed alternative activation markers (Arginase1 and Chitinase 3-like 3) via quantitative RT-PCR and western blots.
  • Investigated TGFβ signaling pathways using receptor inhibitors and measured endogenous TGFβ release.

Main Results:

  • TGFβ significantly enhanced IL4-induced expression of alternative activation markers (Arg1, Ym1) in microglia.
  • This synergistic effect was dependent on TGFβ receptor signaling and partially mediated by MAPK pathways.
  • IL4 treatment induced endogenous TGFβ2 release, and TGFβ alone upregulated IL4 receptor alpha, increasing microglial sensitivity to IL4.

Conclusions:

  • TGFβ plays a novel, crucial role in promoting IL4-induced alternative activation of microglia.
  • These findings highlight TGFβ's function as an anti-inflammatory and immunoregulatory factor in microglia.
  • The study consolidates TGFβ's importance in modulating microglial immune responses within the central nervous system.

More Related Videos

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice07:07

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice

Published on: June 27, 2020

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates09:12

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...