Novel functions of the polymeric Ig receptor: well beyond transport of immunoglobulins

Phalipon, Armelle; Corthésy, Blaise

doi:10.1016/s1471-4906(02)00031-5

Cited by 185 publications

(146 citation statements)

References 31 publications

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“…The precise receptor types and associated signal transduction mechanisms mediating sIgA secretion by these and possibly other enteric neurotransmitters at this mucosal immune effector site remain to be characterized. Both CCh and NE stimulate colonic mucin secretion (Smith and Butler, 1974;Neutra et al, 1984Barcelo et al, 2001; both IgA and SC bind to intestinal mucus and may function in a cooperative fashion with mucus in inhibiting bacterial adherence to the mucosal surface (Bouvet et al, 1993;Phalipon et al, 2003). The functional interrelationships between IgA and mucin secretion as well as other mucosal defense processes which are subject to enteric neuromodulation clearly warrant investigation.…”

Section: Discussionmentioning

confidence: 99%

Autonomic neurotransmitters modulate immunoglobulin A secretion in porcine colonic mucosa

Schmidt

Xie

Lyte

et al. 2007

Journal of Neuroimmunology

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Secretory immunoglobulin A (sIgA) plays a crucial role in mucosal surface defense. We tested the hypothesis that colonic sIgA secretion is under enteric neural control. Immunohistochemistry of the porcine distal colonic mucosa revealed presumptive cholinergic and adrenergic nerve fibers apposed to secretory component (SC)-positive crypt epithelial cells and neighboring IgA + plasmacytes. The cholinomimetic drug carbamylcholine elicited rapid, atropine-sensitive IgA secretion into the luminal fluid bathing mucosal explants mounted in Ussing chambers. The adrenergic receptor agonist norepinephrine also increased IgA secretion, an action inhibited by phentolamine. These effects were independent of agonist-induced anion secretion. In Western blots of luminal fluid, both agonists increased the density of protein bands co-immunoreactive for IgA and SC. Mucosal exposure to enterohemorrhagic Escherichia coli did not affect IgA secretion, and carbamylcholine treatment did not affect mucosal adherence of this enteropathogen. Acetylcholine and norepinephrine, acting respectively through muscarinic cholinergic and alpha-adrenergic receptors in the colonic mucosa, stimulate sIgA secretion and may enhance mucosal defense in vivo.

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Section: Discussionmentioning

confidence: 99%

Autonomic neurotransmitters modulate immunoglobulin A secretion in porcine colonic mucosa

Schmidt

Xie

Lyte

et al. 2007

Journal of Neuroimmunology

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“…In the continuing presence of TNF, which in vivo could also be produced by activated macrophages and T cells recruited to the intestinal mucosa, the program of TNF-induced gene expression may begin to shift from proinflammatory to antiinflammatory. Continued high expression of pIgR would be important in this phase to limit the inflammatory response to bacterial and viral products, for example via epithelial transport of IgA anti-LPS Abs (7), and through the anti-inflammatory effector functions of the secretory component of pIgR (8). It is important to note that gene products traditionally associated with acute inflammatory responses may also play roles in limiting inflammation and promoting tissue repair.…”

Section: Discussionmentioning

confidence: 99%

“…A novel anti-inflammatory function for IgA has been suggested by the demonstration that IgA can neutralize LPS within intestinal epithelial cells during pIgR-mediated transport (7). Secretory component, the cleaved extracellular domain of pIgR, further contributes to intestinal defense and homeostasis by acting as a nonspecific microbial scavenger and by limiting inflammatory processes (8).…”

mentioning

confidence: 99%

Long-Term Exposure of the HT-29 Human Intestinal Epithelial Cell Line to TNF Causes Sustained Up-Regulation of the Polymeric Ig Receptor and Proinflammatory Genes through Transcriptional and Posttranscriptional Mechanisms

Bruno

Kaetzel

2005

The Journal of Immunology

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Transport of IgA Abs across intestinal epithelial cells into gut secretions is mediated by the polymeric Ig receptor (pIgR). The cytokine TNF plays a central role in initiating and amplifying inflammatory reactions, and is implicated in the pathogenesis of inflammatory bowel diseases. Acute exposure of intestinal epithelial cell lines to TNF has been shown to up-regulate transcription of genes encoding pIgR and a number of proinflammatory factors, but the effects of chronic exposure to TNF have not been studied. We found that exposure of HT-29 human colon carcinoma cells to TNF for up to 20 days reduced the rate of cell proliferation, but did not cause gross morphological changes. Expression of mRNA encoding pIgR and several proinflammatory genes increased acutely, and then diminished but remained elevated above control levels throughout the experiment. Changes in gene expression were paralleled by increased expression of the transcription factors IFN regulatory factor-1 and the RelB subunit of NF-κB. HT-29 cells activated the endogenous TNF gene in response to TNF treatment, but the level of TNF production was insufficient to maintain pIgR and proinflammatory gene expression after withdrawal of exogenous TNF. Chronic exposure to TNF caused a marked increase in pIgR mRNA stability and a small but significant decrease in TNF mRNA stability, but no change in the half-lives of IL-8, c-Myc, and GAPDH. In summary, we observed different effects of acute vs chronic exposure to TNF on gene expression, and found evidence for transcriptional and posttranscriptional regulation of expression of the pIgR.

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“…Since pIgR transport occurs continuously and independently of binding of pIgA, free SC is released when unoccupied receptors are cleaved. This free SC exhibits scavenger properties with respect to enteric pathogens [80].…”

Section: Transport Of Piga Into the Mucosal Secretions By The Pigrmentioning

confidence: 99%

The IgA system: a comparison of structure and function in different species

2006

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-The predominant immunoglobulin isotype on most mucosal surfaces is secretory immunoglobulin A (SIgA), a polypeptide complex comprising two IgA monomers, the connecting J chain, and the secretory component. The molecular stability and strong anti-inflammatory properties make SIgA particularly well suited to provide protective immunity to the vulnerable mucosal surfaces by preventing invasion of inhaled and ingested pathogens. In contrast to SIgA, IgA in serum functions as an inflammatory antibody through interaction with FcαR on immune effector cells. Although IgA appears to share common features and protective functions in different species, significant variations exist within the IgA systems of different species. This review will give an overview of the basic concepts underlying mucosal IgA defence which will focus on the variations present among species in structure, antibody repertoire development, pIgR-mediated transport, colostral IgA content, hepatobiliary transport, and function with particular emphasis on the IgA system of the pig and dog. These interspecies variations emphasise the importance of elucidating and analysing the IgA system within the immune system of the species of interest rather than inferring roles from conclusions made in human and mouse studies.

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Novel functions of the polymeric Ig receptor: well beyond transport of immunoglobulins

Cited by 185 publications

References 31 publications

Autonomic neurotransmitters modulate immunoglobulin A secretion in porcine colonic mucosa

Autonomic neurotransmitters modulate immunoglobulin A secretion in porcine colonic mucosa

Long-Term Exposure of the HT-29 Human Intestinal Epithelial Cell Line to TNF Causes Sustained Up-Regulation of the Polymeric Ig Receptor and Proinflammatory Genes through Transcriptional and Posttranscriptional Mechanisms

The IgA system: a comparison of structure and function in different species

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