In Situ Identification of Both IL-4 and IL-10 Cytokine–Receptor Interactions during Tissue Regeneration

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IL-10 was secreted by T-helper Th2 cell clones and inhibited cytokine pro- duction by Th1 cells. IL-10 was also found to be secreted by CD4 and CD8 T cells, B cells,  macrophages, monocytes, dendritic cells (DC), neutrophils, mast cells, eosinophils, and natural killer cells. 

In addition, some non-hematopoietic cells, epithelial cells, and tumor cells could also produce IL-10. IL-10 is a multifunctional cytokine; its main function is to suppress inflammatory responses. In addition, it regulates the function of monocytes, macrophages, B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells. IL-10 is recognized by its cytokine-specific receptor.   

The tissue regeneration phase is characterized by the change in phenotype of M1 macrophages into M2 macrophages that increase in number by producing anti-inflammatory cytokines, such as IL-10 and TGF-β.

IL-4/IL-13 induces polarization of M2a, IL-1R agonists/Toll-like receptor induces polarization of M2b, IL-10 induces polarization of M2c, IL-6 induces polarization of M2d macrophages, in contrast to IFN-γ, TNF, and Lipopolysaccharide (LPS), which induce polarization of M1 macrophages.

In vivo, intramuscular injection of IL-10 DNA is effective in suppressing inflammation by inhibiting the production of proinflammatory cytokines. In addition, IL-10 can promote myocardial cell regeneration and skeletal muscle cell healing. Myocytes are capable of co-expressing IL-10 and IL-10R, but this interaction has not yet been experimentally demonstrated under in situ conditions.  

For IL-10, many IL-10+ cells were identified in skin, lung, and muscle sections. No IL-10 expression was detected in granulocytes.  IL-10 acts by binding to the IL-10R-specific receptor complex. The IL-10/IL-10R interaction is particularly important in modulating immune responses and limiting excessive inflammation. IL-10 has potent anti-inflammatory properties and can inhibit the production of pro-inflammatory cytokines and chemokines. In addition, it plays a role in regulating the activation and function of various immune cells such as macrophages, dendritic cells, and T cells, promoting an anti-inflammatory environment. When IL-10 is present in the tissue or cellular microenvironment, it can bind to the IL-10Rα subunit on the cell surface, leading to the recruitment and association of the IL-10Rβ subunit. 

1. K. Nikovics, A.-L. Favier, M. Rocher, C. Mayinga, J. Gomez, F. Dufour-Gaume, D. Riccobono, In Situ Identification of Both IL-4 and IL-10 Cytokine-Receptor Interactions during Tissue Regeneration. Cells 12 (2023).

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