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Author Spotlight: Achieving High-Purity In Vitro Differentiation of Th17 Cells Using Cytokine Concentration Modulation
Published on: October 25, 2024
Alternaria alternata acts on human Monocyte-derived Dendritic cells to mediate Th2/Th17 polarisation
A Loghmani1, R Raoofi2, A Ownagh2
1Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Introduction:
Although the mechanism of asthma is not precisely understood in humans, clinical and epidemiological studies have offered a potential relationship between exposure to environmental fungi, such as Alternaria alternata (A. alternata) and the development and exacerbation of asthma. The aim of this project is to investigate the mechanisms of Th2 responses by A. alternata as a clinically relevant model for the environmental exposure.
Materials And Methods:
Plastic adherent monocytes were cultured with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) to convert these cells into Monocyte-derived Dendritic cells (MoDc) and then matured in the presence of Monocyte-Conditioned Medium (MCM) as the control group and MCM+ A. alternata extract as the inductive groups.
Results:
The results indicated that the expression of CD14 decreased and CD83 and anti-human leukocyte antigen-DR (HLA-DR) increased in the inductive groups in comparison with the control group. More importantly, A. alternata inhibited IL-12 production by activated dendritic cells (DCs), and the DCs exposed to A. alternata enhanced the Th2 polarisation of CD4+ T cells. The production amount of IL-10 overcame IL-12 as well as Il-23 increased significantly, and hand in T cells the production of cytokines Interferon-γ (IFN-γ) decreased. However, both IL-17 and IL-4 increased (p<0.05). Phagocytic activity in the inductive groups decreased significantly compared with the control group.
Conclusion:
The asthma-related environmental fungus A. alternata, with an effect on dendritic cells profile mediates TH2/TH17. Such immunodysregulation properties of causative environmental fungi may explain their strong relationship with human asthma and allergic diseases.
Insights
Environmental fungus Alternaria alternata exposure influences immune responses, potentially explaining its link to asthma development. This study investigates how A. alternata affects dendritic cells and T cell polarization, revealing key immunodysregulation mechanisms.
Area of Science:
- Immunology
- Environmental Health
Background:
- Asthma mechanisms remain unclear, but environmental fungi like Alternaria alternata are linked to its development and exacerbation.
- Investigating fungal exposure's role in asthma is crucial for understanding disease pathogenesis.
Purpose of the Study:
- To investigate the mechanisms of Th2 (T helper 2) responses induced by Alternaria alternata (A. alternata).
- To utilize A. alternata as a model for environmental exposure in studying asthma-related immune responses.
Main Methods:
- Monocytes were differentiated into Monocyte-derived Dendritic cells (MoDCs).
- MoDCs were matured with Monocyte-Conditioned Medium (MCM) as control or MCM + A. alternata extract.
- Changes in cell surface markers, cytokine production, and phagocytic activity were analyzed.
Main Results:
- A. alternata exposure altered dendritic cell (DC) profiles, decreasing CD14 and increasing CD83 and HLA-DR.
- A. alternata inhibited IL-12 production by DCs and promoted Th2 polarization of CD4+ T cells.
- Increased IL-10 and IL-23, decreased IFN-γ, and increased IL-4 and IL-17 were observed in T cells; phagocytic activity decreased.
Conclusions:
- Alternaria alternata affects dendritic cell profiles, mediating Th2/Th17 responses.
- The immunodysregulation by environmental fungi like A. alternata may explain their association with human asthma and allergic diseases.

