Last update 01 Nov 2024

STAT6 x IL-3 x IL-4

Last update 01 Nov 2024

Basic Info

Related Targets

STAT6IL-3IL-4

Drugs associated with STAT6 x IL-3 x IL-4

KT-621

Target

IL-3 x IL-4 x STAT6

Mechanism

IL-3 inhibitors [+2]

Active Org.

Kymera Therapeutics, Inc.

Originator Org.

Kymera Therapeutics, Inc.

Active Indication

prurigo nodularis [+5]

Inactive Indication-

Drug Highest PhaseIND Approval

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with STAT6 x IL-3 x IL-4

100 Translational Medicine associated with STAT6 x IL-3 x IL-4

0 Patents (Medical) associated with STAT6 x IL-3 x IL-4

Literatures (Medical) associated with STAT6 x IL-3 x IL-4

01 May 2023·Immunology

Interleukin‐3 stabilizes CD124/IL‐4α surface expression in mast cells via Tyk2 and STAT6

Article

Author: Drube, Sebastian ; Andreas, Nico ; Jäger, Ute‐Maria ; Küchler, Claudia ; Strotmann, Birgit ; Wegner, Philine

AbstractInterleukin (IL)‐4 signals can modulate mast cells, which express the IL‐4Rα chain. The IL‐4Rα can heterodimerise with the common γ‐chain and utilizes JAK1 and JAK2 for signal transduction, while complexes of IL‐4Rα with IL‐13Rα1 subunit mediates signals via JAK2 and Tyk2. Here, we report that IL‐3 is an essential factor for the continuous expression of the IL‐4Rα chain on mast cells, which did not express the IL‐13Rα1 chain. We demonstrate that the signals induced by IL‐3 important for IL‐4Rα expression are mediated by Tyk2 and STAT6 activation and the subsequent maintenance of HSP90 levels. In line with that, inhibition of either Tyk2, STAT6 or HSP90 impaired the IL‐3‐induced IL‐4Rα upregulation. Consequently, the IL‐3 maintained IL‐4Rα surface expression via Tyk2 is essential for the costimulatory effect of IL‐4 on the IL‐33‐induced production of IL‐6 and IL‐13.

01 Dec 2019·ImmunologyQ3 · MEDICINE

Siglec‐F is induced by granulocyte–macrophage colony‐stimulating factor and enhances interleukin‐4‐induced expression of arginase‐1 in mouse macrophages

Q3 · MEDICINE

Article

Author: Tateyama, Hiroyuki ; Iijima, Shinji ; Murase, Yusuke ; Nishijima, Ken‐ichi ; Kaneoka, Hidenori ; Inasaka, Yui ; Higuchi, Hiroshi

SummarySiglecs are cell surface lectins that recognize sialic acids and are primarily expressed in hematopoietic cells. Previous studies showed that some Siglecs regulate macrophage function. In the present study, we examined the induction and putative roles of mouse Siglec‐F in bone‐marrow‐derived macrophages in mice. A quantitative RT‐PCR analysis showed that the basal expression of Siglec‐F was weak in bone‐marrow‐derived macrophages differentiated by macrophage colony‐stimulating factor. However, a 24‐hr stimulation with granulocyte–macrophage colony‐stimulating factor (GM‐CSF) enhanced Siglec‐F expression. GM‐CSF also enhanced Siglec‐F expression in thioglycollate‐induced peritoneal macrophages. The inhibition of signal transducer and activator of transcription 5 (STAT5), but not that of phosphoinositide 3‐kinase or mitogen‐activated protein kinase kinase, significantly reduced the induction of Siglec‐F. Interleukin‐3, which uses a common β‐chain shared with the GM‐CSF receptor to stimulate the STAT5 pathway, also enhanced Siglec‐F expression. The knockdown of Siglec‐F by a specific small interfering RNA enhanced GM‐CSF‐induced STAT5 phosphorylation, suggesting that Siglec‐F down‐regulates its own expression upon prolonged GM‐CSF stimulation. Furthermore, the knockdown of Siglec‐F reduced the STAT6 phosphorylation and expression of arginase‐1 in interleukin‐4‐stimulated macrophages. These results suggest that Siglec‐F fine‐tunes the immune responses of macrophages.

01 Apr 2019·Translational ResearchQ2 · MEDICINE

T helper 2 differentiation is necessary for development of lymphedema

Q2 · MEDICINE

Article

Author: Kataru, Raghu P ; Mehrara, Babak J ; Ly, Catherine L ; Nores, Gabriela D García

T cells infiltrating lymphedematous tissues have a mixed T helper 1 (Th1) and Th2 differentiation profile. Treatment with neutralizing antibodies targeting cytokines that promote Th2 differentiation (interleukin 4 [IL-4] and IL-13) decreases the severity of lymphedema in preclinical models, suggesting that Th2 cells play a key role in the pathology of this disease. However, these previous studies do not address the contribution of Th1 cells and it remains unknown if IL-4 and IL-3 blockade acts primarily on T cells or decreases the pathological changes of lymphedema by other mechanisms. Therefore, this study sought to analyze the effect of lymphatic injury in transgenic mice with mutations that cause defects in Th1 and Th2 cell generation (T-bet knockout or T-betKO and STAT6 knockout or STAT6KO mice, respectively). Using both the mouse tail and popliteal lymph node dissection models of lymphedema, we show that Th2-deficient (STAT6KO) mice are protected from developing lymphedema, have decreased fibrosis, increased collateral vessel formation, and preserved collecting lymphatic vessel pumping function. In contrast, mice with defective Th1 cell generation (T-betKO) develop disease with the same severity as wild-type controls. Taken together, our results suggest that Th2 differentiation is necessary for development of lymphedema following lymphatic injury and that Th1 differentiation does not significantly contribute to the pathology of the disease. Such findings are important as immunotherapy directed at Th2 cells has been found to be effective in well-studied Th2-mediated diseases such as asthma and atopic dermatitis and may therefore be similarly useful for lymphedema management.

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