Deletion of mesencephalic astrocyte-derived neurotrophic factor delays and damages the development of white pulp in spleen

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress-induced protein, and it has been reported that ER stress and unfolded protein response (UPR) are closely related to the immune system. The spleen is an important immune organ and we have shown in our previous research that MANF is expressed in human spleen tissues. However, there have been limited studies about the effect of MANF on spleen development. In this study, we detected MANF expression in spleen tissues and found that MANF was expressed in the red pulp and marginal zone. Additionally, MANF was localized in the CD68⁺ and CD138⁺ cells of adult rat spleen tissues, but not in the CD3⁺ cells. We performed immunohistochemical staining to detect MANF expression in the spleen tissues of rats that were different ages, and we found that MANF⁺ cells were localized together in the spleen tissues of rats that were 1–4 weeks old. MANF was also expressed in CD68⁺ cells in the spleen tissues of rats and mice. Furthermore, we found that MANF deficiency inhibited white pulp development in MANF knockout mice, thus indicating that MANF played an important role in the white pulp development of rodent spleen tissues.