Exercise improves intestinal IgA production by T-dependent cell pathway in adults but not in aged mice

Abstract

IntroductionHypermutated high-affinity immunoglobulin A (IgA), neutralizes toxins and drives the diversification of bacteria communities to maintain intestinal homeostasis although the mechanism underlies the impact of moderate aerobic exercise (MAE) on the IgA-generation via T-dependent (TD) is not fully know. Therefore, the aim of this study was to determine the effect of long-time MAE on the production of IgA through the TD pathway in Peyer´s patches of the small intestine from aged mice.MethodsMAE protocol consisted of twenty 3-month-old (young) BALB/c mice running in an endless band at 0° inclination and a speed of 10 m/h for 5 days a week and resting 2 days on the weekend until reaching 6-month-old (adulthood, n=10) or 24-month-old (aging, n=10). Groups of young, adult, or elderly mice were included as sedentary controls (n=10/per group). At 6 or 24 months old, all were sacrificed, and small intestine samples were dissected to prepare intestinal lavages for IgA quantitation by ELISA and to obtain suspensions from Peyer´s patches (PP) and lamina propria (LP) cells for analysis of T, B, and plasma cell subpopulations by flow cytometry and mRNA analysis expression by RT-qPCR of molecular factors related to differentiation of B cells to IgA+ plasma cells, class switch recombination, and IgA-synthesis. Statistical analysis was computed with two-way ANOVA (factor A=age, factor B=group) and p<0.05 was considered for statistically significant differences.ResultsCompared to age-matched sedentary control, in exercised elderly mice, parameters were either increased (IgA concentration, IL-21, IL-10 and RDH mRNA expression), decreased (α-chain mRNA, B cells, mIgA+ B cells, mIgM+ B cells and IL-4 mRNA) or unchanged (PP mIgA+ plasmablasts and LP cyt-IgA+ plasma cells). Regarding the exercised adult mice, they showed an up-modulation of IgA-concentration, mRNA expression IL-21, IL-10, and RDH and cells (PP B and T cells, mIgM+ plasmablasts and LP cyt-IgA+plasma cells).ConclusionOur findings suggest that MAE restored the IgA production in adult mice via the TD cell pathway but does not in aged mice. Other studies are necessary to know in more detail the impact of long-time MAE on the TD pathway to produce IgA in aging.

Moderate Aerobic Exercise Induces the Homeostatic IgA Generation in Senile Mice

“…These findings suggested that MAE improved the intestinal response by enhancing the APRIL mRNA level associated with the T-cell independent pathway of B cell response committed for an increase of IgA generation. Findings support the impact of MAE on the increase (twofold) of intestinal IgA concentration in aged mice by comparison with senile sedentary mice [33].…”

“…In addition, the loss of Pax5 levels during terminal differentiation contributes to the plasma cell transcription program to IgA CSR [9]. In spite of the plasma cell number was unchanged by the exercise, in this study increased luminal IgA concentration (previously reported [33] ), and α-chain mRNA level found in exercised mice may result from the decrease of Pax5 mRNA favoring both the IgA plasma cell surviving and IgA CSR.…”

“…Thus, data suggested that MAE drives divergent B cell responses in aged and adult mice according to B cell maturity. A recent contribution from our group of study [33], indicated that MAE increased the intestinal IgA antibody concentration via T-cell dependent only in adult mice. In senile mice, MAE induced the increase of homeostatic IgA presumably via microbiota modulation [33].…”

“…A recent contribution from our group of study [33], indicated that MAE increased the intestinal IgA antibody concentration via T-cell dependent only in adult mice. In senile mice, MAE induced the increase of homeostatic IgA presumably via microbiota modulation [33]. In the current assay, interestingly, MAE only enhanced APRIL mRNA levels in senile mice whereas elicited TSLP, APRIL, BAFF, and RDH mRNA levels in adult mice.…”

“…The impact of aging on pIgR expression has been evidenced in dYY mice (with high monomeric IgA concentration in serum and low monomeric IgA concentration in urine) associated with defective pIgR-mediated IgA transport [22]. In a previous study luminal IgA increase in senile exercised mice was seen (33); in the current study pIgR mRNA was found decreased what suggested that the luminal IgA concentration increases independent of pIgR-mediated IgA-transcytosis Pro-inflammatory cytokines including IFN-γ, TNFα, and IL-4 favor pIgR mRNA expression, thus data suggested then that, MAE under senescence conditions down-modulates these proinflammatory cytokines and upmodulates the anti-inflammatory cytokines such as IL-10 and TGF-β. Therefore, MAE may provide a beneficial impact in aging by both ameliorating the cytokines that participate in the inflammatory process and by increasing the luminal IgA via independent pIgR-mediated IgA-transcytosis.…”