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Canonical (CD74/CD44) and Non-Canonical (CXCR2, 4 and 7) MIF Receptors Are Differentially Expressed in Rheumatoid
Gabriela Athziri Sánchez-Zuno1, Richard Bucala2, Jorge Hernández-Bello1
1Instituto de Investigación en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco 44340, Mexico.
Abstract:
Macrophage migration inhibitory factor (MIF) significantly contributes to rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate the canonical (CD74/CD44) and non-canonical MIF receptors (CXCR2,4 and 7) expression and sCD74 to establish their association with RA clinical activity according to DAS28-ESR.
Methodology:
101 RA patients with different clinical activities (remission (n = 27), low (n = 16), moderate (n = 35) and high (n = 23)) and 9 control subjects (CS) were included. Expression was evaluated by flow cytometry and levels of soluble CD74 (sCD74) by ELISA. Data analysis was performed with FlowJov10.0, STATAv12.0, and GraphPad Prism v7.0.
Results:
According to disease activity, CXCR7 expression (percentage of expression and mean fluorescence intensity (MFI)) was higher in granulocytes from patients in remission, while the expression of CXCR4 was higher in patients with high disease activity (p < 0.05). The expression of CD74 was higher in B cells (p < 0.05) and monocytes (p < 0.01) from patients in remission. Regarding sCD74 levels these were higher in patients with high disease activity when compared to those in remission (p <0.05).
Conclusions:
The results support the need for further study of the role of sCD74 as a soluble MIF decoy receptor, sequestering it to negatively regulate MIF signaling though its membrane receptors. The expression patterns of CXCR4 and CXCR7 show that the latter is a scavenger-type receptor that prevents endocytosis and even degradation of CXCR4 under inflammatory conditions.
Insights
Soluble CD74 (sCD74) levels correlate with rheumatoid arthritis (RA) disease activity. CXCR4 and CXCR7 receptor expression patterns in RA patients offer insights into macrophage migration inhibitory factor (MIF) signaling pathways.
Area of Science:
- Immunology
- Rheumatology
- Molecular Biology
Background:
- Macrophage migration inhibitory factor (MIF) is a key factor in rheumatoid arthritis (RA) pathogenesis.
- Understanding MIF receptor expression is crucial for RA treatment strategies.
Purpose of the Study:
- To evaluate the expression of canonical (CD74/CD44) and non-canonical (CXCR2, CXCR4, CXCR7) MIF receptors.
- To assess soluble CD74 (sCD74) levels in relation to RA clinical activity (DAS28-ESR).
Main Methods:
- Included 101 RA patients with varying disease activity and 9 controls.
- Flow cytometry was used to evaluate receptor expression.
- ELISA measured sCD74 levels; statistical analysis performed using FlowJo, STATAv12.0, and GraphPad Prism.
Main Results:
- CXCR7 expression was higher in granulocytes of RA patients in remission.
- CXCR4 expression was higher in patients with high RA disease activity.
- CD74 expression was elevated in B cells and monocytes of patients in remission, while sCD74 levels were higher in those with high disease activity.
Conclusions:
- sCD74 may act as a decoy receptor, negatively regulating MIF signaling.
- CXCR4 and CXCR7 expression patterns suggest CXCR7 functions as a scavenger receptor, influencing CXCR4 stability under inflammation.
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