The fellowship of regulatory and tissue-resident memory cells

Barros, Leandro; Ferreira, Cristina; Veldhoen, Marc

doi:10.1038/s41385-021-00456-w

Cited by 23 publications

(19 citation statements)

References 137 publications

(185 reference statements)

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“…S3Y ). Regulatory T cells expressing Tbet or RORγt have been proposed as counter-regulators of inflammatory Th1 and Th17 cells, respectively (Barros et al, 2022; Yang et al, 2016). Consistent with this, the abundance of Tbet + Treg cells follow the same trends as inflammatory Th1 cells with higher levels in FF-fed, SM14-colonized mice ( Fig 3H and S5E) .…”

Section: Resultsmentioning

confidence: 99%

Opposing diet, microbiome and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host

Pereira

Boudaud

Wolter

et al. 2022

Preprint

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Inflammatory bowel disease (IBD) is a chronic condition characterized by periods of spontaneous intestinal inflammation and is increasing in industrialized populations. Combined with host genetic predisposition, both diet and gut bacteria are thought to be prominent environmental features contributing to IBD, but little is known about the precise mechanisms. We show that low dietary fiber promotes bacterial erosion of the protective colonic mucus layer, leading to lethal colitis in interleukin-10-deficient mice. This diet-induced inflammation is specifically driven by mucin-degrading bacteria-mediated Th1 immune responses and is preceded by expansion of natural killer T cells and reduced immunoglobulin A coating of specific bacterial species. Low fiber, exclusive enteral nutrition reduced disease in part by increasing bacterial production of the metabolite isobutyrate, which was dependent on the presence of soy protein in the diet. Our results highlight a mechanistic framework to unravel the complex web of potentially opposing diet, host and microbial factors that combine to influence IBD development.

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Section: Resultsmentioning

confidence: 99%

Opposing diet, microbiome and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host

Pereira

Boudaud

Wolter

et al. 2022

Preprint

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“…Since CD69+CD103+ T cells were observed at 15 weeks post- LmCen -/- immunization at which point we could not recover any viable parasites, it is unlikely that these cells are CD4+ T Reg cells that require the presence of persistent infection ( 36 ). Additionally, the residency of T Reg cells in the non-lymphoid organs in the absence of persistent infection is not fully understood ( 37 , 38 ). Future studies will delineate the roles of T Reg and TRM cells in LmCen -/- vaccine-induced immunity.…”

Section: Discussionmentioning

confidence: 99%

Leishmania Major Centrin Gene-Deleted Parasites Generate Skin Resident Memory T-Cell Immune Response Analogous to Leishmanization

et al. 2022

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Leishmaniasis is a vector-borne parasitic disease transmitted through the bite of a sand fly with no available vaccine for humans. Recently, we have developed a live attenuated Leishmania major centrin gene-deleted parasite strain (LmCen-/-) that induced protection against homologous and heterologous challenges. We demonstrated that the protection is mediated by IFN (Interferon) γ-secreting CD4+ T-effector cells and multifunctional T cells, which is analogous to leishmanization. In addition, in a leishmanization model, skin tissue-resident memory T (TRM) cells were also shown to be crucial for host protection. In this study, we evaluated the generation and function of skin TRM cells following immunization with LmCen-/- parasites and compared those with leishmanization. We show that immunization with LmCen-/- generated skin CD4+ TRM cells and is supported by the induction of cytokines and chemokines essential for their production and survival similar to leishmanization. Following challenge with wild-type L. major, TRM cells specific to L. major were rapidly recruited and proliferated at the site of infection in the immunized mice. Furthermore, upon challenge, CD4+ TRM cells induce higher levels of IFNγ and Granzyme B in the immunized and leishmanized mice than in non-immunized mice. Taken together, our studies demonstrate that the genetically modified live attenuated LmCen-/- vaccine generates functional CD4+ skin TRM cells, similar to leishmanization, that may play a crucial role in host protection along with effector T cells as shown in our previous study.

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“…Intriguingly, in this regard, IL-15 has been known to modulate microbial communities (44); therefore, it is plausible that a high IL-15 expression might alter the microbiome in PLE. This can lead to the generation of microbe-and/or microbial antigen-specific skin Trm, and the (re)activation of such cells, therefore, could have broader implications, e.g., launching inappropriate responses against external antigens and contributing to the chronicity of the disease (45,46). Moreover, IL-15 is known to induce macrophage differentiation and trigger cathelicidin peptide (LL-37) (47).…”

Section: Discussionmentioning

confidence: 99%

Accumulation of Cytotoxic Skin Resident Memory T Cells and Increased Expression of IL-15 in Lesional Skin of Polymorphic Light Eruption

et al. 2022

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Patients with polymorphic light eruption (PLE) develop lesions upon the first exposure to sun in spring/summer, but lesions usually subside during season due to the natural (or medical) photohardening. However, these lesions tend to reappear the following year and continue to do so in most patients, suggesting the presence of a disease memory. To study the potential role of skin resident memory T cells (Trm), we investigated the functional phenotype of Trm and the expression of IL-15 in PLE. IL-15 is known to drive Trm proliferation and survival. Multiplex immunofluorescence was used to quantify the expression of CD3, CD4, CD8, CD69, CD103, CD49a, CD11b, CD11c, CD68, granzyme B (GzmB), interferon-gamma (IFN-γ), and IL-15 in formalin-fixed, paraffin-embedded lesional skin samples from PLE patients and healthy skin from control subjects. Unlike the constitutive T cell population in healthy skin, a massive infiltration of T cells in the dermis and epidermis was observed in PLE, and the majority of these belonged to CD8+ T cells which express Trm markers (CD69, CD103, CD49a) and produced cytotoxic effector molecules GzmB and IFN-γ. Higher numbers of CD3+ T cells and CD11b+CD68+ macrophages produced IL-15 in the dermis as compared to healthy skin. The dominant accumulation of cytotoxic Trm cells and increased expression of IL-15 in lesional skin of PLE patients strongly indicates the potential role of skin Trm cells in the disease manifestation and recurrence.

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The fellowship of regulatory and tissue-resident memory cells

Cited by 23 publications

References 137 publications

Opposing diet, microbiome and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host

Opposing diet, microbiome and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host

Leishmania Major Centrin Gene-Deleted Parasites Generate Skin Resident Memory T-Cell Immune Response Analogous to Leishmanization

Accumulation of Cytotoxic Skin Resident Memory T Cells and Increased Expression of IL-15 in Lesional Skin of Polymorphic Light Eruption

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