Related Experiment Video

Updated: May 9, 2026

Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel
07:26

Ferric Chloride-induced Thrombosis Mouse Model on Carotid Artery and Mesentery Vessel

Published on: June 29, 2015

Tpl2 kinase regulates FcγR signaling and immune thrombocytopenia in mice

Irene Kyrmizi1, Marianna Ioannou, Maria Hatziapostolou

  • 12.Div. of Allergy, Clinical Immunology and Rheumatology, New York Medical College, 40 Sunshine Cottage Rd., Valhalla, NY 10595, USA. Ioannis_Tassiulas@nymc.edu.

Journal of Leukocyte Biology
|July 31, 2013
PubMed

Insights

The Tpl2 protein regulates immune responses. Inhibiting Tpl2 protects mice from autoimmune conditions like immune thrombocytopenia (ITP) by blocking harmful platelet destruction.

Area of Science:

  • Immunology
  • Molecular Biology
  • Autoimmunity

Background:

  • The MAPK3 Tpl2 kinase is a key regulator of innate and adaptive immunity, influencing Toll-like receptor (TLR), tumor necrosis factor-alpha (TNF-α), and G-protein coupled receptor (GPCR) signaling.
  • Tpl2 deficiency results in an anti-inflammatory phenotype, conferring resistance to endotoxin shock, colitis, and inflammatory bowel disease (IBD).

Purpose of the Study:

  • To investigate the role of Tpl2 in the development of autoimmune diseases.
  • To determine if Tpl2 inhibition can protect against immune thrombocytopenia (ITP).

Main Methods:

  • Utilized mouse models with Tpl2 ablation (genetic knockout) and pharmacological inhibition.
  • Induced antiplatelet antibody-mediated thrombocytopenia, a model for ITP.
  • Analyzed FcγR signaling pathways in splenic and hepatic myeloid cells, focusing on Tpl2 activation, ERK signaling, calcium influx, and gene expression.

Main Results:

  • Ablation and pharmacological inhibition of Tpl2 significantly protected mice from developing antiplatelet antibody-induced thrombocytopenia.
  • Thrombocytopenia in this model is driven by FcγR-mediated phagocytosis of antibody-opsonized platelets by myeloid cells.
  • Tpl2 is activated by FcγR signaling in macrophages, and this activation is crucial for downstream ERK activation, calcium influx, cytokine/coreceptor gene induction, and subsequent phagocytosis.

Conclusions:

  • Tpl2 plays a critical role in FcγR-mediated phagocytosis and the pathogenesis of autoimmune thrombocytopenia.
  • Pharmacological inhibition of Tpl2 represents a potential therapeutic strategy for treating ITP and potentially other FcγR-driven autoimmune disorders.
Keywords:
MAPKimmune complexmacrophages

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors

Published on: July 17, 2020

Related Concept Videos

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...