Immune receptor may be key to hay fever treatment

A recent study of immune system receptors in mice may lead to the development of new clinical treatments for some immune disorders, including hay fever, asthma, and eczema.

To protect the host, the immune system must recognize and react to invading pathogens. Sometimes, however, the immune system overreacts to nonthreatening environmental substances or to host tissues, causing allergies and autoimmune disorders, respectively. Many of these 'hypersensitivity reactions' are mediated by type 2 T-helper (T_h2) cells; instances of T_h2-induced hypersensitivity may be alleviated if a type 1 T-helper (T_h1) cell response is induced instead.

In research published in the August issue of Nature Immunology, a team of researchers led by Shizuo Akira at Osaka University in Japan may have found a way to 'turn on' the T_h1 response in lieu of the T_h2. They made this discovery during their investigation of the in vivo function of the toll-like receptor 5 (TLR5). TLRs are proteins found on many immune cells that help to activate those cells in response to certain pathogens. TLR5 receptors, which are commonly found in the intestine, are activated by recognition of the protein flagellin, the main component of bacterial flagella.

Akira's team created Tlr5-knockout mice and then used microarray analysis to compare the cytokine expression profiles between the intestinal cells in the knockout and wild-type mice after exposure to flagellin. The researchers focused on a particular type of cells called CD11c⁺ lamina propria cells (LPCs), which are located just beneath the intestinal epithelium. They found that the wild-type murine CD11c⁺ LPCs (which express TRL5) produced the pro-inflammatory cytokine IL-12, which is essential for inducing a T_h1 immune response; the knockout mice failed to produce such a response, leading the researchers to conclude that flagellin was able to induce TLR5-mediated IL-12 secretion in the CD11c⁺ LPCs.

According to the paper's first author, Satoshi Uematsu, these findings support the possibility that CD11c⁺ LPCs might serve as targets for immunostimulatory therapies. “Having shown that CD11c⁺ LPCs induce inflammatory responses via TLR5,” Uematsu tells Lab Animal, “we want to try and stimulate these cells with flagellin in vivo in order to induce a T_h1 immune response for treatment of hay fever or cancer immune therapy.” To this end, Uematsu asserts that he and his colleagues now are trying to isolate human LPCs.