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      Immune Cell Subtypes and Their Function in the Testis

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          Abstract

          Immunoregulation in the testis is characterized by a balance between immuno-suppression (or immune privilege) and the ability to react to infections and inflammation. In this review, we analyze the phenotypes of the various immune cell subtypes present in the testis, and how their functions change between homeostatic and inflammatory conditions. Starting with testicular macrophages, we explore how this heterogeneous population is shaped by the testicular microenvironment to ensure immune privilege. We then describe how dendritic cells exhibit a tolerogenic status under normal conditions, but proliferate, mature and then stimulate effector T-cell expansion under inflammatory conditions. Finally, we outline the two T-cell populations in the testis: CD4 +/CD8 + αβ T cells and CD4 +/CD8 + Foxp3 + regulatory T cells and describe the distribution and function of mast cells. All these cells help modulate innate immunity and regulate the immune response. By improving our understanding of immune cell behavior in the testis under normal and inflammatory conditions, we will be better placed to evaluate testis impairment due to immune mechanisms in affected patients.

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          Most cited references65

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          Tissue-resident macrophage enhancer landscapes are shaped by the local microenvironment.

          Macrophages are critical for innate immune defense and also control organ homeostasis in a tissue-specific manner. They provide a fitting model to study the impact of ontogeny and microenvironment on chromatin state and whether chromatin modifications contribute to macrophage identity. Here, we profile the dynamics of four histone modifications across seven tissue-resident macrophage populations. We identify 12,743 macrophage-specific enhancers and establish that tissue-resident macrophages have distinct enhancer landscapes beyond what can be explained by developmental origin. Combining our enhancer catalog with gene expression profiles and open chromatin regions, we show that a combination of tissue- and lineage-specific transcription factors form the regulatory networks controlling chromatin specification in tissue-resident macrophages. The environment is capable of shaping the chromatin landscape of transplanted bone marrow precursors, and even differentiated macrophages can be reprogrammed when transferred into a new microenvironment. These results provide a comprehensive view of macrophage regulatory landscape and highlight the importance of the microenvironment, along with pioneer factors in orchestrating identity and plasticity.
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            A lineage of myeloid cells independent of Myb and hematopoietic stem cells.

            Macrophages and dendritic cells (DCs) are key components of cellular immunity and are thought to originate and renew from hematopoietic stem cells (HSCs). However, some macrophages develop in the embryo before the appearance of definitive HSCs. We thus reinvestigated macrophage development. We found that the transcription factor Myb was required for development of HSCs and all CD11b(high) monocytes and macrophages, but was dispensable for yolk sac (YS) macrophages and for the development of YS-derived F4/80(bright) macrophages in several tissues, such as liver Kupffer cells, epidermal Langerhans cells, and microglia--cell populations that all can persist in adult mice independently of HSCs. These results define a lineage of tissue macrophages that derive from the YS and are genetically distinct from HSC progeny.
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              Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches

              Macrophages are a heterogeneous cell population involved in tissue homeostasis, inflammation, and various pathologies. Although the major tissue-resident macrophage populations have been extensively studied, interstitial macrophages (IMs) residing within the tissue parenchyma remain poorly defined. Here we studied IMs from murine lung, fat, heart, and dermis. We identified two independent IM subpopulations that are conserved across tissues: Lyve1 lo MHCII hi CX3CR1 hi (Lyve1 lo MHCII hi ) and Lyve1 hi MHCII lo CX3CR1 lo (Lyve1 hi MHCII lo ) monocyte-derived IMs, with distinct gene expression profiles, phenotypes, functions, and localizations. Using a new mouse model of inducible macrophage depletion ( Slco2b1 flox/DTR ), we found that the absence of Lyve1 hi MHCII lo IMs exacerbated experimental lung fibrosis. Thus, we demonstrate that two independent populations of IMs coexist across tissues and exhibit conserved niche-dependent functional programming.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                30 September 2020
                2020
                : 11
                : 583304
                Affiliations
                [1] 1 Department of Anatomy and Cell Biology, Justus-Liebig University Giessen , Giessen, Germany
                [2] 2 Hessian Center of Reproductive Medicine, Justus-Leibig-University Giessen , Giessen, Germany
                [3] 3 Departamento de Biología Celular e Histología/Unidad Académica II, Facultad de Medicina, Universidad de Buenos Aires (UBA) , Buenos Aires, Argentina
                [4] 4 Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Medicina, Instituto de Investigaciones Biomédicas (INBIOMED), Universidad de Buenos Aires (UBA) , Buenos Aires, Argentina
                [5] 5 Medical Research Center, The First Affiliated Hospital of Zhengzhou University , Zhengzhou, China
                Author notes

                Edited by: Kenneth Tung, University of Virginia, United States

                Reviewed by: Tony DeFalco, Cincinnati Children’s Hospital Medical Center, United States; Suresh Yenugu, University of Hyderabad, India; Emily Bryan, Queensland University of Technology, Australia

                This article was submitted to Mucosal Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2020.583304
                7554629
                33101311
                35cb15e5-e5cc-4dd1-95d0-694649958ab4
                Copyright © 2020 Bhushan, Theas, Guazzone, Jacobo, Wang, Fijak, Meinhardt and Lustig

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 July 2020
                : 14 September 2020
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 65, Pages: 7, Words: 3204
                Funding
                Funded by: Deutsche Forschungsgemeinschaft 10.13039/501100001659
                Award ID: BH93 (1-4), GRK 1871/2-1
                Categories
                Immunology
                Mini Review

                Immunology
                testis,immune privilege,macrophages,dendritic cells,t lymphocytes,mast cells
                Immunology
                testis, immune privilege, macrophages, dendritic cells, t lymphocytes, mast cells

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