IL-35, as an inhibitory cytokine, plays an important role in infectious diseases. The study suggested that Mycobacterium tuberculosis (M. tuberculosis) could induce T cell proliferation and foster IFN-γ production in p35-deficient mice, P40 deficient mice, and wild-type mice, thus eliminating the pathogen. Mice lacking p40 have been found to be less able to show antigen-specific responses than those lacking the p35 subunit. However, their ability to counteract infection is less pronounced than that of wild-type mice [
42]. In addition, the protective responses can be induced in wild-type and p35-deficient mice by inoculating with vaccines, and increased the secretion of IFN-γ and IL-17. However, P40-deficient mice did not produce antigen-specific IFN-γ or IL-17, and increased the infection load of bacteria. In addition, treatment of p35-deficient mice with
Candida albicans (
C. albicans) reduced the rate of fungal infection and was associated with little to no obvious symptoms of infection relative to P19-deficient mice. In p35-deficient mice and those in which p35 gene was disrupted, the immunosuppressive function of IL-35 was inhibited, which impaired anti-fungal immunity [
43]. The CD4
+ T cells in the peripheral blood of patients with chronic hepatitis B also showed high levels of expression of p35 and EB13 protein, indicating that IL-35 was related to the immune response of chronic hepatitis B patients [
44]. These results showed that, during the acute infection process, IL-35 preferentially activated Th1 cells, stimulated proliferation of Treg cells, and inhibited the differentiation of Th17 cells, thereby preventing excessive tissue damage caused by the clearing of pathogens. In the chronic infection and inflammation, IL-35 selectively inhibited effector cells, including Th17 cells, which slowed down the development of autoimmune diseases [
1]. (Fig.
4).