Age-related chemokine alterations affect IgA secretion and gut immunity in female mice
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RESEARCH ARTICLE
Age-related chemokine alterations affect IgA secretion and gut immunity in female mice Hideyuki Nagafusa . Kazutoshi Sayama
Received: 21 January 2020 / Accepted: 30 March 2020 Ó Springer Nature B.V. 2020
Abstract 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 ageassociated 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
H. Nagafusa K. Sayama Graduate School of Integrated Science and Technology, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan K. Sayama (&) College of Agriculture, Academic Institute, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan e-mail: [email protected]
CCL25 production and increase in colonic CCL28 production c be involved in aging-associated deterioration of gut immunity. Keywords CCL25 CCL28 Aging Gut immunity IgA
Introduction The gastrointestinal mucosal surface is a major site of the immune response, as this site is exposed to many food-derived proteins, pathogens and commensal microbes, underscoring the importance of gut immunity in normal physiology. The immunoglobulin A (IgA) antibody plays essential roles in gut immunity, regulating the mucosal immune response and maintaining the microbiome. Secretory IgA is produced by IgA-ASCs (IgA-antibody secreting cell) and released into the intestinal lumen. Secretory IgA maintains the intestinal microbial balance by antigen binding (Mantis et al. 2011). Moreover, a recent study identified that intestinal IgA activates portions of the gut microbiome, promoting protection from inflammation (Nakajima et al. 2018). Immune function is well-known to decline with aging (Schmucker et al. 2003), increasing the risk of infections of the gut (Moretto et al. 2008). Ageassociated depletion of the IgA response is thought to contribute to declining intestinal immunity. However,
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Biogerontology
this mechanism is still not completely elucidated. The number of naive T-cells, which play important roles in differentiation of IgA-ASCs in the Peyer’s patch, are decreased during aging
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