Researchers at Children’s Hospital of Philadelphia (CHOP) have discovered that a specific type of lung cell exhibits unconventional immune properties and may contribute to the outcome of respiratory viral infections. The researchers focused on type II alveolar (AT2) cells, which are non-immune cells of the lung that are critical for basic lung health and tissue repair after lung injury. They found that AT2 cells express high levels of major histocompatibility complex II (MHC-II), an important immune system trigger, and that AT2 MHC-II expression appears to confer an appreciable advantage in the outcome of respiratory viral infection. The findings were published today in Nature Communications.
“This study shows that MHC-II expression is regulated in a unique way in AT2 cells, which has important implications for the health of lungs when faced with infection,” said senior author Laurence Eisenlohr, VMD, PhD, investigator and Professor of Pathology and Laboratory Medicine at CHOP. “Future research should explore whether alterations in AT2 MHC-II expression or function contribute to the wide variation in outcome of lung diseases in humans, particularly SARS-CoV-2 infection, as AT2s are a major cell type infected with this virus in the human lung.”
MHC-II triggers an immune cascade that activates helper T cells, which in turn drive B cells, cytotoxic T cells and other important immune cells required to fight an infection. The sequence begins when a peptide from the infectious pathogen connects with MHC-II protein, and that complex is presented on the surface of the cell, a process known as “antigen presentation.” Historically, only certain types of specialized immune cells, termed “professional antigen presenting cells,” have been shown to express MHC-II at steady state, including B cells, dendritic cells, and macrophages; other cells outside of the immune system are thought to express MHC-II only when inflammation is present, such as during an infection. However, recent research has shown that some of these other “non-immune” cell types, including AT2s, can also express MHC-II under normal conditions as well, and this is thought to be driven by small amounts of inflammation that are still present even at homeostasis.
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