1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The cellular and immunological dynamics of early and transitional human milk

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Human milk is essential for infant nutrition and immunity, providing protection against infections and other immune-mediated diseases during the lactation period and beyond in later childhood. Milk contains a broad range of bioactive factors such as nutrients, hormones, enzymes, immunoglobulins, growth factors, cytokines, and antimicrobial factors, as well as heterogeneous populations of maternal cells. The soluble and cellular components of milk are dynamic over time to meet the needs of the growing infant. In this study, we utilize systems-approaches to define and characterize 62 analytes of the soluble component, including immunoglobulin isotypes, as well as the cellular component of human milk during the first two weeks postpartum from 36 mothers. We identify soluble immune and growth factors that are dynamic over time and could be utilized to classify milk into different phenotypic groups. We identify 24 distinct populations of both epithelial and immune cells by single-cell transcriptome analysis of 128,016 human milk cells. We found that macrophage populations have shifting inflammatory profiles during the first two weeks of lactation. This analysis provides key insights into the soluble and cellular components of human milk and serves as a substantial resource for future studies of human milk.

          Abstract

          The cellular and immunological dynamics of early and transitional human milk are characterised, providing a key resource for future research.

          Related collections

          Most cited references47

          • Record: found
          • Abstract: not found
          • Article: not found

          Cytokines, inflammation, and pain.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Specificity and affinity of human Fcgamma receptors and their polymorphic variants for human IgG subclasses.

            Distinct genes encode 6 human receptors for IgG (hFcgammaRs), 3 of which have 2 or 3 polymorphic variants. The specificity and affinity of individual hFcgammaRs for the 4 human IgG subclasses is unknown. This information is critical for antibody-based immunotherapy which has been increasingly used in the clinics. We investigated the binding of polyclonal and monoclonal IgG1, IgG2, IgG3, and IgG4 to FcgammaRI; FcgammaRIIA, IIB, and IIC; FcgammaRIIIA and IIIB; and all known polymorphic variants. Wild-type and low-fucosylated IgG1 anti-CD20 and anti-RhD mAbs were also examined. We found that (1) IgG1 and IgG3 bind to all hFcgammaRs; (2) IgG2 bind not only to FcgammaRIIA(H131), but also, with a lower affinity, to FcgammaRIIA(R131) and FcgammaRIIIA(V158); (3) IgG4 bind to FcgammaRI, FcgammaRIIA, IIB and IIC and FcgammaRIIIA(V158); and (4) the inhibitory receptor FcgammaRIIB has a lower affinity for IgG1, IgG2, and IgG3 than all other hFcgammaRs. We also identified parameters that determine the specificity and affinity of hFcgammaRs for IgG subclasses. These results document how hFcgammaR specificity and affinity may account for the biological activities of antibodies. They therefore highlight the role of specific hFcgammaRs in the therapeutic and pathogenic effects of antibodies in disease.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Structure and function of immunoglobulins.

              Immunoglobulins are heterodimeric proteins composed of 2 heavy and 2 light chains. They can be separated functionally into variable domains that bind antigens and constant domains that specify effector functions, such as activation of complement or binding to Fc receptors. The variable domains are created by means of a complex series of gene rearrangement events and can then be subjected to somatic hypermutation after exposure to antigen to allow affinity maturation. Each variable domain can be split into 3 regions of sequence variability termed the complementarity-determining regions (CDRs) and 4 regions of relatively constant sequence termed the framework regions. The 3 CDRs of the heavy chain are paired with the 3 CDRs of the light chain to form the antigen-binding site, as classically defined. The constant domains of the heavy chain can be switched to allow altered effector function while maintaining antigen specificity. There are 5 main classes of heavy chain constant domains. Each class defines the IgM, IgG, IgA, IgD, and IgE isotypes. IgG can be split into 4 subclasses, IgG1, IgG2, IgG3, and IgG4, each with its own biologic properties, and IgA can similarly be split into IgA1 and IgA2. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
                Bookmark

                Author and article information

                Contributors
                tcbradley@cmh.edu
                Journal
                Commun Biol
                Commun Biol
                Communications Biology
                Nature Publishing Group UK (London )
                2399-3642
                18 May 2023
                18 May 2023
                2023
                : 6
                : 539
                Affiliations
                [1 ]GRID grid.512054.7, Genomic Medicine Center, , Children’s Mercy Research Institute, Children’s Mercy Kansas City, ; Kansas City, MO 64108 USA
                [2 ]GRID grid.412016.0, ISNI 0000 0001 2177 6375, Department of Pathology and Laboratory Medicine, , University of Kansas Medical Center, ; Kansas City, KS 66160 USA
                [3 ]GRID grid.239559.1, ISNI 0000 0004 0415 5050, Division of Neonatology, , Children’s Mercy Kansas City, ; Kansas City, MO 64108 USA
                [4 ]GRID grid.239559.1, ISNI 0000 0004 0415 5050, Fetal Health Center, Children’s Mercy Kansas City, ; Kansas City, MO 64108 USA
                [5 ]GRID grid.266756.6, ISNI 0000 0001 2179 926X, Department of Pediatrics, , UMKC School of Medicine, ; Kansas City, MO 64108 USA
                [6 ]GRID grid.412016.0, ISNI 0000 0001 2177 6375, Department of Pediatrics, , University of Kansas Medical Center, ; Kansas City, KS 66160 USA
                Author information
                http://orcid.org/0000-0001-7319-0237
                http://orcid.org/0000-0001-9326-3245
                http://orcid.org/0000-0002-0582-3220
                http://orcid.org/0000-0002-1601-631X
                Article
                4910
                10.1038/s42003-023-04910-2
                10195133
                36596887
                41c5f401-80e4-408c-a0be-beb8dfcfd45b
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 September 2022
                : 3 May 2023
                Categories
                Article
                Custom metadata
                © Springer Nature Limited 2023

                mucosal immunology,immunogenetics
                mucosal immunology, immunogenetics

                Comments

                Comment on this article