Stimulation by food proteins plays a critical role in the maturation of the immune system

Menezes, José Elmo de; Mucida, Daniel; Cara, Denise Carmona; Alvarez-Leite, Jacqueline I; Russo, Marco; Vaz, Nelson M.; Faria, Ana Maria Caetano

doi:10.1093/intimm/dxg043

Cited by 93 publications

(37 citation statements)

References 35 publications

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“…However, induced IEL differentiation appears to be driven by exogenous antigen rather than self-antigen, and these cells may therefore be the antigen-specific “adaptive” counterparts of innate-like natural IELs (Mucida et al, 2013). Consistent with a role of antigen in this process, germ-free mice and mice fed an elementary diet free of protein antigens show decreased intestinal IEL numbers (Bandeira et al, 1990; Menezes et al, 2003; Helgeland et al, 1996; Umesaki et al, 1993). …”

Section: The Spectrum Of Tissue-resident Lymphocytesmentioning

confidence: 85%

Hallmarks of Tissue-Resident Lymphocytes

Fan

Rudensky

2016

Cell

301

258

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Although they are classically viewed as continuously recirculating through the lymphoid organs and blood, lymphocytes also establish residency in non-lymphoid tissues, most prominently at barrier sites, including the mucosal surfaces and skin. These specialized tissue-resident lymphocyte subsets span the innate-adaptive continuum and include innate lymphoid cells (ILCs), unconventional T cells (e.g., NKT, MAIT, γδ T cells, and CD8αα+IELs), and tissue-resident memory T (TRM) cells. Although these diverse cell types differ in the particulars of their biology, they nonetheless exhibit important shared features, including a role in the preservation of tissue integrity and function during homeostasis, infection, and non-infectious perturbations. In this Review, we discuss the hallmarks of tissue-resident innate, innate-like, and adaptive lymphocytes, as well as their potential functions in non-lymphoid organs.

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Section: The Spectrum Of Tissue-resident Lymphocytesmentioning

confidence: 85%

Hallmarks of Tissue-Resident Lymphocytes

Fan

Rudensky

2016

Cell

301

258

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“…[4] Similar to microbial depletion, animals receiving an elemental antigen diet also fail to develop CD8αα + IELs. [77] Tryptophan-derived ligands that are produced as metabolites from cruciferous vegetables bind to the aryl hydrocarbon receptor (AhR); this receptor is highly expressed on CD8αα + and γδ IELs and is required for their survival. [78] As a result, AhR knockout mice demonstrate increased susceptibility to experimental colitis due to an expanded induced colonic IEL population and microbial overgrowth.…”

Section: Dietary Factors Contributing To Ibd Adversely Affect Naturalmentioning

confidence: 99%

Sentinels at the Frontline: the Role of Intraepithelial Lymphocytes in Inflammatory Bowel Disease

Edelblum

2017

Curr Pharmacol Rep

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Purpose of review Intestinal mucosal immunity is tightly regulated to ensure effective host defense against invasive microorganisms while limiting the potential for aberrant damage. In inflammatory bowel disease (IBD), an imbalance between effector and regulatory T cell populations results in an uncontrolled inflammatory response to commensal bacteria. Intraepithelial lymphocytes (IEL) are perfectly positioned within the intestinal epithelium to provide the first line of mucosal defense against luminal microbes or rapidly respond to epithelial injury. This review will highlight how IELs promote protective intestinal immunity and discuss the evidence indicating that altered IEL responses contribute to the pathogenesis of IBD. Recent findings Although the role of IELs in mucosal homeostasis has been largely underappreciated, many of the same factors that contribute to the dysregulation of host defense in IBD also adversely affect IELs. For example, IL-23 and the endoplasmic reticulum stress response can enhance IEL lytic activity toward enterocytes. Microbial dysbiosis or defective microbial recognition results in the loss of regulatory IELs, further amplifying these pro-inflammatory effects. Migration of T cells into or within the intraepithelial compartment has a profound effect on their differentiation or effector function demonstrating that IELs are exquisitely sensitive to changes in the local intestinal microenvironment. Summary Enhanced mechanistic insight into the regulation of IEL survival, differentiation and effector function may provide useful tools to modulate IEL surveillance or enhance IEL regulatory function. Elucidation of these processes may result in the development of novel therapeutics to reduce intestinal inflammation and reinforce the mucosal barrier in IBD.

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“…This large lymphocyte-rich surface contacts daily an equally large collection of natural antigens coming from two sources: gut microbiota and diet. It is estimated that we eat 190 g of protein antigens daily and that the number of bacteria colonizing the human intestine is around 10 12 bacteria/g of stool (98). Thus, the gut microbiota provides a variety of antigenic components continuously, and a significant part of the dietary proteins reaches the circulation in its intact immunogenic form (99) (Box 3).…”

Section: Gut Microbiota–host Interactions and Oral Tolerance: When Thmentioning

confidence: 99%

Towards a Liquid Self: How Time, Geography, and Life Experiences Reshape the Biological Identity

et al. 2014

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The conceptualization of immunological self is amongst the most important theories of modern biology, representing a sort of theoretical guideline for experimental immunologists, in order to understand how host constituents are ignored by the immune system (IS). A consistent advancement in this field has been represented by the danger/damage theory and its subsequent refinements, which at present represents the most comprehensive conceptualization of immunological self. Here, we present the new hypothesis of “liquid self,” which integrates and extends the danger/damage theory. The main novelty of the liquid self hypothesis lies in the full integration of the immune response mechanisms into the host body’s ecosystems, i.e., in adding the temporal, as well as the geographical/evolutionary and environmental, dimensions, which we suggested to call “immunological biography.” Our hypothesis takes into account the important biological changes occurring with time (age) in the IS (including immunosenescence and inflammaging), as well as changes in the organismal context related to nutrition, lifestyle, and geography (populations). We argue that such temporal and geographical dimensions impinge upon, and continuously reshape, the antigenicity of physical entities (molecules, cells, bacteria, viruses), making them switching between “self” and “non-self” states in a dynamical, “liquid” fashion. Particular attention is devoted to oral tolerance and gut microbiota, as well as to a new potential source of unexpected self epitopes produced by proteasome splicing. Finally, our framework allows the set up of a variety of testable predictions, the most straightforward suggesting that the immune responses to defined molecules representing potentials antigens will be quantitatively and qualitatively quite different according to the immuno-biographical background of the host.

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Stimulation by food proteins plays a critical role in the maturation of the immune system

Cited by 93 publications

References 35 publications

Hallmarks of Tissue-Resident Lymphocytes

Hallmarks of Tissue-Resident Lymphocytes

Sentinels at the Frontline: the Role of Intraepithelial Lymphocytes in Inflammatory Bowel Disease

Towards a Liquid Self: How Time, Geography, and Life Experiences Reshape the Biological Identity

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