Related Experiment Video

Updated: Feb 8, 2026

Murine Model of Epicutaneously-Induced Immunomodulation
09:07

Murine Model of Epicutaneously-Induced Immunomodulation

Published on: June 24, 2025

560

Integrin, alpha9 subunit blockade suppresses collagen-induced arthritis with minimal systemic immunomodulation

Shingo Sugahara1, Kaori Hanaoka1, Nobuchika Yamamoto1

  • 1Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.

European Journal of Pharmacology
|June 23, 2018
PubMed

Insights

Blocking alpha9, a novel target for rheumatoid arthritis (RA), suppressed arthritis development in mice by reducing fibroblast-like synoviocyte activation. This approach shows promise for joint inflammation therapy with minimal immune system impact.

Area of Science:

  • Immunology
  • Rheumatology
  • Molecular Biology

Background:

  • Integrin, alpha9 subunit (alpha9) is overexpressed in rheumatoid arthritis (RA) joints and preclinical models, preceding symptom onset.
  • Alpha9 is identified as a novel therapeutic target for RA due to its elevated expression in affected tissues.

Purpose of the Study:

  • To evaluate the pharmacological profile of an anti-alpha9 antibody in a collagen-induced arthritis (CIA) mouse model.
  • To investigate the mechanism of action for alpha9 blockade in arthritis, focusing on fibroblast-like synoviocyte (FLS) activation and immune responses.

Main Methods:

  • Administration of an anti-alpha9 antibody in CIA mice.
  • Assessment of arthritis development, plasma biomarkers, antibody formation, and immune cell populations in joints and spleen.
  • Evaluation of alpha9's role in mixed lymphocyte reaction (MLR) and delayed type hypersensitivity (DTH) in non-arthritic mice.

Main Results:

  • Anti-alpha9 antibody treatment suppressed arthritis development and decreased FLS-derived biomarkers in CIA mice.
  • Alpha9 blockade reduced immune cell accumulation in arthritic joints but not in the spleen.
  • No inhibitory effect of alpha9 blockade was observed in MLR or DTH reactions in non-arthritic mice.
  • Therapeutic administration of anti-alpha9 antibody alleviated established arthritis.

Conclusions:

  • Alpha9 blockade exerts anti-arthritic effects by suppressing FLS activation through a non-immune mediated mechanism.
  • Targeting alpha9 offers a promising therapeutic strategy for joint inflammation in RA with minimal systemic immunomodulation.
  • Anti-alpha9 therapy is effective in both preventing and treating established arthritis in a preclinical model.
Keywords:
Fibroblast-like synoviocyteIntegrin, alpha9 subunitNon-immune responseRheumatoid arthritis

More Related Videos

A Cryo-pulverization Protocol for Processing Mouse Paws to Evaluate Molecular Pathways of Tissue Inflammation in a Collagen Induced Arthritis Model11:03

A Cryo-pulverization Protocol for Processing Mouse Paws to Evaluate Molecular Pathways of Tissue Inflammation in a Collagen Induced Arthritis Model

Published on: October 30, 2019

9.1K
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo12:42

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

10.2K

Related Concept Videos

Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
5.5K
Neuromuscular Junction And Blockade01:29

Neuromuscular Junction And Blockade

The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
5.1K
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
5.1K
Fibril-associated Collagen01:11

Fibril-associated Collagen

Fibril-associated collagens are a type of collagens present in the extracellular matrix with interrupted triple helices or FACIT (Fibril-associated collagens interrupted triple-helices). FACIT help connect and attach the collagen fibrils with each other as well as with other proteins of the extracellular matrix.
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
3.4K
Second Order systems II01:18

Second Order systems II

In an underdamped second-order system, where the damping ratio ζ is between 0 and 1, a unit-step input results in a transfer function that, when transformed using the inverse Laplace method, reveals the output response. The output exhibits a damped sinusoidal oscillation, and the difference between the input and output is termed the error signal. This error signal also demonstrates damped oscillatory behavior. Eventually, as the system reaches a steady state, the error diminishes to zero.
412
First Order Systems01:21

First Order Systems

First-order systems, such as RC circuits, are foundational in understanding dynamic systems due to their straightforward input-output relationship. Analyzing their responses to different input functions under zero initial conditions reveals significant insights into system behavior.
When a first-order system is subjected to a unit-step input, its response is characterized by its transfer function. By applying the Laplace transform of the unit-step input to the transfer function, expanding the...
433