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Intestinal Microfold Cells Play a Critical Role in the Uptake and Oral Tolerance Mediated by Lysophosphatidylserine-Containing Lipidic Nanoparticles.

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Title: Intestinal Microfold Cells Play a Critical Role in the Uptake and Oral Tolerance Mediated by Lysophosphatidylserine-Containing Lipidic Nanoparticles.
Authors: Chak, Vincent1 (AUTHOR), Harne, Sujay1,2 (AUTHOR), Kay, Jason G.2,3 (AUTHOR), Wohlfert, Elizabeth1,3 (AUTHOR), Balu-Iyer, Sathy V.1,2 (AUTHOR) svb@buffalo.edu
Source: Nanomaterials (2079-4991). Apr2026, Vol. 16 Issue 7, p412. 19p.
Subjects: M cells, Phosphatidylserines, Immune system, Immunological tolerance, Lymphoid tissue, Liposomes
Abstract: Phosphatidylserine (PS) is an anionic phospholipid that is exposed to the outer leaflet of the cell membrane during apoptosis. This PS externalization can teach the immune system to tolerate an antigen without eliciting immunological consequences. Previously, we showed that mice treated with PS nanoparticles containing single-chain PS (LysoPS) induced oral tolerance towards therapeutic proteins, whereas double-chain PS did not. These observations suggest that structural alterations of PS play a critical role in its tolerogenic potential. Given that intestinal microfold cells (M-cells) facilitate the transport of particulate antigens from the intestinal lumen to Peyer's patches (PP) for immune surveillance, we hypothesized that the failure of double-chain PS to induce tolerance may result from insufficient uptake by M-cells. The M cell-mediated uptake was investigated using in vitro and ex vivo studies and oral tolerance towards ovalbumin (OVA) was studied in M-cell-deficient mice. Consistent with this hypothesis, our data showed that LysoPS nanoparticles displayed at least a 2-fold increase in immune cell exposure and M-cell-mediated uptake compared to double-chain PS-containing nanoparticles. Importantly, LysoPS-mediated oral tolerance was absent in M cell-deficient mice with higher anti-ova antibody titers than the wild-type strain. These studies demonstrate that higher PS exposure on LysosPS nanoparticles compared to double chain could play a significant role in M cell-mediated tolerance. [ABSTRACT FROM AUTHOR]
Copyright of Nanomaterials (2079-4991) is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
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  Data: Intestinal Microfold Cells Play a Critical Role in the Uptake and Oral Tolerance Mediated by Lysophosphatidylserine-Containing Lipidic Nanoparticles.
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  Data: <searchLink fieldCode="AR" term="%22Chak%2C+Vincent%22">Chak, Vincent</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Harne%2C+Sujay%22">Harne, Sujay</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kay%2C+Jason+G%2E%22">Kay, Jason G.</searchLink><relatesTo>2,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wohlfert%2C+Elizabeth%22">Wohlfert, Elizabeth</searchLink><relatesTo>1,3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Balu-Iyer%2C+Sathy+V%2E%22">Balu-Iyer, Sathy V.</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> svb@buffalo.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Nanomaterials+%282079-4991%29%22">Nanomaterials (2079-4991)</searchLink>. Apr2026, Vol. 16 Issue 7, p412. 19p.
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  Data: <searchLink fieldCode="DE" term="%22M+cells%22">M cells</searchLink><br /><searchLink fieldCode="DE" term="%22Phosphatidylserines%22">Phosphatidylserines</searchLink><br /><searchLink fieldCode="DE" term="%22Immune+system%22">Immune system</searchLink><br /><searchLink fieldCode="DE" term="%22Immunological+tolerance%22">Immunological tolerance</searchLink><br /><searchLink fieldCode="DE" term="%22Lymphoid+tissue%22">Lymphoid tissue</searchLink><br /><searchLink fieldCode="DE" term="%22Liposomes%22">Liposomes</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Phosphatidylserine (PS) is an anionic phospholipid that is exposed to the outer leaflet of the cell membrane during apoptosis. This PS externalization can teach the immune system to tolerate an antigen without eliciting immunological consequences. Previously, we showed that mice treated with PS nanoparticles containing single-chain PS (LysoPS) induced oral tolerance towards therapeutic proteins, whereas double-chain PS did not. These observations suggest that structural alterations of PS play a critical role in its tolerogenic potential. Given that intestinal microfold cells (M-cells) facilitate the transport of particulate antigens from the intestinal lumen to Peyer's patches (PP) for immune surveillance, we hypothesized that the failure of double-chain PS to induce tolerance may result from insufficient uptake by M-cells. The M cell-mediated uptake was investigated using in vitro and ex vivo studies and oral tolerance towards ovalbumin (OVA) was studied in M-cell-deficient mice. Consistent with this hypothesis, our data showed that LysoPS nanoparticles displayed at least a 2-fold increase in immune cell exposure and M-cell-mediated uptake compared to double-chain PS-containing nanoparticles. Importantly, LysoPS-mediated oral tolerance was absent in M cell-deficient mice with higher anti-ova antibody titers than the wild-type strain. These studies demonstrate that higher PS exposure on LysosPS nanoparticles compared to double chain could play a significant role in M cell-mediated tolerance. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Nanomaterials (2079-4991) is the property of MDPI and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Text: English
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      – SubjectFull: Liposomes
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      – TitleFull: Intestinal Microfold Cells Play a Critical Role in the Uptake and Oral Tolerance Mediated by Lysophosphatidylserine-Containing Lipidic Nanoparticles.
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            NameFull: Chak, Vincent
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              M: 04
              Text: Apr2026
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              Y: 2026
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