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      Neutrophil‐T cell crosstalk and the control of the host inflammatory response

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          Summary

          While fundamental in their innate role in combating infection and responding to injury, neutrophils are emerging as key modulators of adaptive immune responses. Such functions are attained via both soluble and nonsoluble effectors that enable at least two major downstream outcomes: first, to mediate and control acute inflammatory responses and second, to regulate adaptive immunity and ultimately promoting the development and maintenance of immune tolerance either by releasing immuno‐modulatory factors, including cytokines, or by directly interacting with cells of the adaptive immune system. Herein, we review these novel properties of neutrophils and redefine the pathophysiological functions of these fascinating multi‐tasking cells, exploring the different mechanisms through which neutrophils are able to either enhance and orchestrate T cell pro‐inflammatory responses or inhibit T cell activity to maintain immune tolerance.

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          Most cited references140

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          Neutrophil extracellular traps kill bacteria.

          Neutrophils engulf and kill bacteria when their antimicrobial granules fuse with the phagosome. Here, we describe that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria. These neutrophil extracellular traps (NETs) degrade virulence factors and kill bacteria. NETs are abundant in vivo in experimental dysentery and spontaneous human appendicitis, two examples of acute inflammation. NETs appear to be a form of innate response that binds microorganisms, prevents them from spreading, and ensures a high local concentration of antimicrobial agents to degrade virulence factors and kill bacteria.
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            Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation

            PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-L1) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads to the inhibition of T cell receptor–mediated lymphocyte proliferation and cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting cells, including human peripheral blood monocytes stimulated with interferon γ, and activated human and murine dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues such as heart and lung. The relative levels of inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation.
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              Polarization of tumor-associated neutrophil phenotype by TGF-beta: "N1" versus "N2" TAN.

              TGF-beta blockade significantly slows tumor growth through many mechanisms, including activation of CD8(+) T cells and macrophages. Here, we show that TGF-beta blockade also increases neutrophil-attracting chemokines, resulting in an influx of CD11b(+)/Ly6G(+) tumor-associated neutrophils (TANs) that are hypersegmented, more cytotoxic to tumor cells, and express higher levels of proinflammatory cytokines. Accordingly, following TGF-beta blockade, depletion of these neutrophils significantly blunts antitumor effects of treatment and reduces CD8(+) T cell activation. In contrast, in control tumors, neutrophil depletion decreases tumor growth and results in more activated CD8(+) T cells intratumorally. Together, these data suggest that TGF-beta within the tumor microenvironment induces a population of TAN with a protumor phenotype. TGF-beta blockade results in the recruitment and activation of TANs with an antitumor phenotype.
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                Author and article information

                Contributors
                s.nadkarni@qmul.ac.uk
                m.perretti@qmul.ac.uk
                Journal
                Immunol Rev
                Immunol Rev
                10.1111/(ISSN)1600-065X
                IMR
                Immunological Reviews
                John Wiley and Sons Inc. (Hoboken )
                0105-2896
                1600-065X
                03 November 2022
                March 2023
                : 314
                : 1 , Neutrophils and Friends ( doiID: 10.1111/imr.v314.1 )
                : 36-49
                Affiliations
                [ 1 ] The William Harvey Research Institute Queen Mary University of London London UK
                Author notes
                [*] [* ] Correspondence

                Mauro Perretti and Suchita Nadkarni, Centre for Biochemical Pharmacology, The William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UK.

                Email: m.perretti@ 123456qmul.ac.uk and s.nadkarni@ 123456qmul.ac.uk

                Author information
                https://orcid.org/0000-0003-2068-3331
                Article
                IMR13162 IMR-2022-075.R2
                10.1111/imr.13162
                10952212
                36326214
                becc6f2f-1ff1-4d49-a8c2-47ba2ed722ce
                © 2022 The Authors. Immunological Reviews published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Figures: 1, Tables: 0, Pages: 14, Words: 11541
                Funding
                Funded by: British Heart Foundation , doi 10.13039/501100000274;
                Award ID: FS/17/1/32528
                Award ID: FS/4yPhD/F/20/34133
                Funded by: Medical Research Council , doi 10.13039/501100007155;
                Award ID: MR/P026362/1
                Categories
                Invited Review
                Invited Reviews
                Custom metadata
                2.0
                March 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.9 mode:remove_FC converted:20.03.2024

                autoimmunity,immune‐mediated diseases,immunosuppression,inflammation,pregnancy

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