<b>TGF-β3 derived from</b><b> </b><b>CD8</b>^{<strong>+</strong>}<b> T</b><b> cells </b><b>plays</b><b> an important role in the lungs of piglets infected with </b><b>SIV</b>

<p dir="ltr">The swine is considered an important host for the production of pandemic influenza viruses, and studying the immune characteristics of swine influenza virus (SIV) infection in piglets is crucial for pandemic prevention. Here, we used single-cell sequencing (scRNA-seq) to demonstrate that Genotype 4 (G4) reassigned Eurasian avian-like (EA) H1N1 SIV and H9N2 avian influenza virus (AIV) infection caused significant changes in immune cell composition, gene expression and cell communication. Our study revealed that H1N1 SIV elicits a stronger immune response, and the number of T cells, especially CD8⁺ T cells, is significantly reduced by infection. Additionally, H1N1 SIV enhanced part of the intercellular communication, especially triggering the T cell-involved transforming growth factor-β (TGF-β) signaling pathway network, in which the activation of TGF-β3 ligand receptor signaling is a key regulator. Moreover, flow cytometry and ELISA analysis revealed that H1N1 SIV infection resulted in an increase in TGF-β3 derived from CD4⁺ and CD8⁺ T cells. The loss of CD8⁺ T cells can slow weight loss and lung inflammation in the early stage of infection but also affects recovery in the later stage of infection. Overall, these results discovered the presence of TGF-β3, which is rarely mentioned in SIV infection, and clarified the importance of the CD8⁺ T-cell balance in infection. This study reveals the effects of H1N1 SIV infection on the composition and function of immune cells, and provides new insights into the prevention and treatment of SIV and the prevention of human pandemics.</p>