Age-related chemokine alterations affect IgA secretion and gut immunity in female mice

The chemokines CCL25 and CCL28, which promote immune cell migration, are primarily expressed in the small and large intestines and play critical roles in sustaining gut immunity. In particular, these chemokines are closely related to intestinal IgA secretion. However, there is no research regarding the effects of aging on CCL25 and CCL28 expression and function. Therefore, in the present study, we investigated the effects of aging on production of CCL25 and CCL28, and on gut immunity, especially IgA secretion, using young and aged female mice. By aging, the levels of small intestinal mRNA and protein of CCL25 lowered, while these levels of CCL28 in colon became higher. Moreover, the number of IgA-antibody secreting cells (IgA-ASCs) and total IgA concentration decreased in the small intestine due to the age-associated reduction of CCL25. In contrast, colonic IgA production was increased due to up-regulation of CCL28, while the number of colonic IgA-ASCs was unchanged with aging. These results clearly demonstrate that aging-associated decrease in small intestinal CCL25 production and increase in colonic CCL28 production c be involved in aging-associated deterioration of gut immunity.