Preferential enhancement of B cell IgA secretion by intestinal epithelial cell-derived cytokines and interleukin-2

Abstract

Intestinal epithelial cells (IEC) are known to secrete a number of important cytokines. Recently, we determined that IEC-derived IL-6 and TGF-beta could enhance IgA secretion and suppress IgM secretion by isolated mucosal B cells. However, since the IEC-derived cytokines must function in the context of locally produced T cell cytokines, the effect of IEC- and T cell-derived cytokines on mucosal B cell immunoglobulin secretion was determined. Using 4 day culture supernatants (IEC-SN) from the rat IEC-6 intestinal epithelial cell line and lipopolysaccharide (LPS) stimulated Peyer's patch or mesenteric lymph node B cells, the IEC- SN was found to act with IL-2 to greatly enhance IgA secretion but limit or suppress IgM secretion as compared to cultures of LPS stimulated B cells alone. However, neither IL-4, IL- 5, nor IFN-gamma affected IgA secretion with the IEC-SN. Depletion of the IEC-SN with specific anti-cytokine antibodies suggested that IEC-derived TGF-beta and IL-6 were both responsible for the enhancing effect along with IL-2 on IgA secretion, whereas IEC-derived TGF-beta alone limited or suppressed IgM secretion. These results suggest that cytokines derived from local IEC and T cells may create an environment which may contribute to the preferential enhancement of IgA secretion seen in mucosal tissues.

Effect of Lactobacillus paracasei CNCM I‐1572 on symptoms, gut microbiota, short chain fatty acids, and immune activation in patients with irritable bowel syndrome: A pilot randomized clinical trial

“…We assessed the fecal levels of IL6, IL8, IL12, TNF‐α, and IFN‐γ, which are typical Th‐1 pro‐inflammatory cytokines, and TGF‐β and IL10, regulatory cytokines capable of suppressing inflammatory responses 30 . In addition to its well‐known pro‐inflammatory role, IL6 also possesses anti‐inflammatory properties exerted through its ability to stimulate IgA secretion 31 , 32 . This evidence may explain why, in our study, the significant decrease in IL6 levels is also accompanied by a decrease in fecal IgA levels after treatment with LCDG, but not placebo 31 , 32 .…”

Postbiotic L. plantarum RG14 improves ruminal epithelium growth, immune status and upregulates the intestinal barrier function in post-weaning lambs

“…In the present study, higher production of IL-6 mRNA was observed in the postbiotic group indicating the activation of humoral immune response which assists B cells in mounting potent antibody responses 46 . This can also be related to higher production and secretion of IgA by the B-cells in the mucosa of jejunum 47–49 . The cytokines involved in pro-inflammatory response such as IL-1β and IL-6 were reported to induce the production of cytokines that enhance the immune response 50 .…”

Genomic and phenotypic evidence for probiotic influences ofLactobacillus gasserion human health

“…Mucosal IgA secretion is mediated by epithelial cytokines, being elicited by transforming growth factor (TGF)-b and potentiated by IL-6 ( Fig. 5) (Goodrich & McGee, 1999). Taken together, these studies highlight the potential of both live and heat-killed L. gasseri to influence the host immune system.…”

“…These cytokines may contribute to the proliferation and differentiation of natural killer (NK) cells, which was observed in the analysis of splenic NK cells from mice fed L. gasseri TMC0356. 5) (Goodrich & McGee, 1999). Purified microbial RNA also suppressed CD4 + T cells, suggesting that nucleic acids of L. gasseri may play a role in immunomodulation (Yoshida et al, 2011).…”