Discovery immunologyPub Date : 2023-08-10eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad013
Heather M Wilson
{"title":"Modulation of macrophages by biophysical cues in health and beyond.","authors":"Heather M Wilson","doi":"10.1093/discim/kyad013","DOIUrl":"10.1093/discim/kyad013","url":null,"abstract":"<p><p>Macrophages play a key role in tissue development and homeostasis, innate immune defence against microbes or tumours, and restoring homeostasis through tissue regeneration following infection or injury. The ability to adopt such diverse functions is due to their heterogeneous nature, which is driven largely by their developmental origin and their response to signals they encounter from the microenvironment. The most well-characterized signals driving macrophage phenotype and function are biochemical and metabolic. However, the way macrophages sense and respond to their extracellular biophysical environment is becoming increasingly recognized in the field of mechano-immunology. These biophysical cues can be signals from tissue components, such as the composition and charge of extracellular matrix or topography, elasticity, and stiffness of the tissue surrounding cells; and mechanical forces such as shear stress or stretch. Macrophages are important in determining whether a disease resolves or becomes chronic. Ageing and diseases such as cancer or fibrotic disorders are associated with significant changes in the tissue biophysical environment, and this provides signals that integrate with those from biochemical and metabolic stimuli to ultimately dictate the overall function of macrophages. This review provides a brief overview of macrophage polarization, followed by a selection of commonly recognized physiological and applied biophysical stimuli impacting macrophage activity, and the potential signalling mechanisms driving downstream responses. The effects of biophysical cues on macrophages' function in homeostasis and disease and the associated clinical implications are also highlighted.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyad013"},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43369152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Discovery immunologyPub Date : 2023-07-20eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad010
Anna Veronika Hipp, Bertram Bengsch, Anna-Maria Globig
{"title":"Friend or Foe - Tc17 cell generation and current evidence for their importance in human disease.","authors":"Anna Veronika Hipp, Bertram Bengsch, Anna-Maria Globig","doi":"10.1093/discim/kyad010","DOIUrl":"10.1093/discim/kyad010","url":null,"abstract":"<p><p>The term <i>Tc17 cells</i> refers to interleukin 17 (IL-17)-producing CD8<sup>+</sup> T cells. While IL-17 is an important mediator of mucosal defense, it is also centrally involved in driving the inflammatory response in immune-mediated diseases, such as psoriasis, multiple sclerosis, and inflammatory bowel disease. In this review, we aim to gather the current knowledge on the phenotypic and transcriptional profile, the <i>in vitro</i> and <i>in vivo</i> generation of Tc17 cells, and the evidence pointing towards a relevant role of Tc17 cells in human diseases such as infectious diseases, cancer, and immune-mediated diseases.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyad010"},"PeriodicalIF":0.0,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41618643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Discovery immunologyPub Date : 2023-07-19eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad008
Ye Chean Teh, Ming Yao Chooi, Shu Zhen Chong
{"title":"Behind the monocyte's mystique: uncovering their developmental trajectories and fates.","authors":"Ye Chean Teh, Ming Yao Chooi, Shu Zhen Chong","doi":"10.1093/discim/kyad008","DOIUrl":"10.1093/discim/kyad008","url":null,"abstract":"<p><p>Monocytes are circulating myeloid cells that are derived from dedicated progenitors in the bone marrow. Originally thought of as mere precursors for the replacement of tissue macrophages, it is increasingly clear that monocytes execute distinct effector functions and may give rise to monocyte-derived cells with unique properties from tissue-resident macrophages. Recently, the advent of novel experimental approaches such as single-cell analysis and fate-mapping tools has uncovered an astonishing display of monocyte plasticity and heterogeneity, which we believe has emerged as a key theme in the field of monocyte biology in the last decade. Monocyte heterogeneity is now recognized to develop as early as the progenitor stage through specific imprinting mechanisms, giving rise to specialized effector cells in the tissue. At the same time, monocytes must overcome their susceptibility towards cellular death to persist as monocyte-derived cells in the tissues. Environmental signals that preserve their heterogenic phenotypes and govern their eventual fates remain incompletely understood. In this review, we will summarize recent advances on the developmental trajectory of monocytes and discuss emerging concepts that contributes to the burgeoning field of monocyte plasticity and heterogeneity.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyad008"},"PeriodicalIF":0.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47813442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Discovery immunologyPub Date : 2023-07-19eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad009
Stefano A P Colombo, Sheila L Brown, Matthew R Hepworth, Jenny Hankinson, Felice Granato, Semra J Kitchen, Tracy Hussell, Angela Simpson, Peter C Cook, Andrew S MacDonald
{"title":"Comparative phenotype of circulating versus tissue immune cells in human lung and blood compartments during health and disease.","authors":"Stefano A P Colombo, Sheila L Brown, Matthew R Hepworth, Jenny Hankinson, Felice Granato, Semra J Kitchen, Tracy Hussell, Angela Simpson, Peter C Cook, Andrew S MacDonald","doi":"10.1093/discim/kyad009","DOIUrl":"10.1093/discim/kyad009","url":null,"abstract":"<p><p>The lung is a dynamic mucosal surface constantly exposed to a variety of immunological challenges including harmless environmental antigens, pollutants, and potentially invasive microorganisms. Dysregulation of the immune system at this crucial site is associated with a range of chronic inflammatory conditions including asthma and Chronic Pulmonary Obstructive Disease (COPD). However, due to its relative inaccessibility, our fundamental understanding of the human lung immune compartment is limited. To address this, we performed flow cytometric immune phenotyping of human lung tissue and matched blood samples that were isolated from 115 donors undergoing lung tissue resection. We provide detailed characterization of the lung mononuclear phagocyte and T cell compartments, demonstrating clear phenotypic differences between lung tissue cells and those in peripheral circulation. Additionally, we show that CD103 expression demarcates pulmonary T cells that have undergone recent TCR and IL-7R signalling. Unexpectedly, we discovered that the immune landscape from asthmatic or COPD donors was broadly comparable to controls. Our data provide a much-needed expansion of our understanding of the pulmonary immune compartment in both health and disease.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"2 1","pages":"kyad009"},"PeriodicalIF":0.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9952332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Discovery immunologyPub Date : 2023-06-24eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad007
Arlisa Alisjahbana, Imran Mohammad, Yu Gao, Elza Evren, Tim Willinger
{"title":"Single-cell RNA sequencing of human lung innate lymphoid cells in the vascular and tissue niche reveals molecular features of tissue adaptation.","authors":"Arlisa Alisjahbana, Imran Mohammad, Yu Gao, Elza Evren, Tim Willinger","doi":"10.1093/discim/kyad007","DOIUrl":"10.1093/discim/kyad007","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) are sentinels of healthy organ function, yet it is unknown how ILCs adapt to distinct anatomical niches within tissues. Here, we used a unique humanized mouse model, MISTRG mice transplanted with human hematopoietic stem and progenitor cells (HSPCs), to define the gene signatures of human ILCs in the vascular versus the tissue (extravascular) compartment of the lung. Single-cell RNA sequencing in combination with intravascular cell labeling demonstrated that heterogeneous populations of human ILCs and natural killer (NK) cells occupied the vascular and tissue niches in the lung of HSPC-engrafted MISTRG mice. Moreover, we discovered that niche-specific cues shape the molecular programs of human ILCs in the distinct sub-anatomical compartments of the lung. Specifically, extravasation of ILCs into the lung tissue was associated with the upregulation of genes involved in the acquisition of tissue residency, cell positioning within the lung, sensing of tissue-derived signals, cellular stress responses, nutrient uptake, and interaction with other tissue-resident immune cells. We also defined a core tissue signature shared between human ILCs and NK cells in the extravascular space of the lung, consistent with imprinting by signals from the local microenvironment. The molecular characterization of human ILCs and NK cells in the vascular and tissue niches of the lung provides new knowledge on the mechanisms of ILC tissue adaptation and represents a resource for further studies.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyad007"},"PeriodicalIF":0.0,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11034571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41850609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Discovery immunologyPub Date : 2023-04-18eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad005
Andrew Muir, Alex Bennett, Hannah Smith, Larisa Logunova, Andrew Wolfenden, Jonathan Fenn, Ann E Lowe, Andy Brass, John R Grainger, Joanne E Konkel, Janette E Bradley, Iris Mair, Kathryn J Else
{"title":"The wild mouse bone marrow has a unique myeloid and lymphoid composition and phenotype.","authors":"Andrew Muir, Alex Bennett, Hannah Smith, Larisa Logunova, Andrew Wolfenden, Jonathan Fenn, Ann E Lowe, Andy Brass, John R Grainger, Joanne E Konkel, Janette E Bradley, Iris Mair, Kathryn J Else","doi":"10.1093/discim/kyad005","DOIUrl":"10.1093/discim/kyad005","url":null,"abstract":"<p><p>The murine bone marrow has a central role in immune function and health as the primary source of leukocytes in adult mice. Laboratory mice provide a human-homologous, genetically manipulable and reproducible model that has enabled an immeasurable volume of high-quality immunological research. However, recent research has questioned the translatability of laboratory mouse research into humans and proposed that the exposure of mice to their wild and natural environment may hold the key to further immunological breakthroughs. To date, there have been no studies providing an in-depth cellular analysis of the wild mouse bone marrow. This study utilized wild mice from an isolated island population (Isle of May, Scotland, UK) and performed flow cytometric and histological analysis to characterize the myeloid, lymphoid, hematopoietic progenitor, and adipocyte compartments within the wild mouse bone marrow. We find that, compared to laboratory mouse bone marrow, the wild mouse bone marrow differs in every cell type assessed. Some of the major distinctions include; a smaller B cell compartment with an enriched presence of plasma cells, increased proportions of KLRG1+ CD8+ T cells, diminished CD11b expression in the myeloid lineage and a five-fold enlargement of the eosinophil compartment. We conclude that the wild mouse bone marrow is dramatically distinct from its laboratory counterparts, with multiple phenotypes that to our knowledge have never been observed in laboratory models. Further research into these unique features may uncover novel immunological mechanisms and grant a greater understanding of the role of the immune system in a natural setting.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyad005"},"PeriodicalIF":0.0,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44544870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Discovery immunologyPub Date : 2023-02-18eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad004
Bethany C Kennedy, Isaac Dean, David R Withers
{"title":"Migration of stem-like CD8 T cells between tissue microenvironments underpins successful anti-tumour immune responses.","authors":"Bethany C Kennedy, Isaac Dean, David R Withers","doi":"10.1093/discim/kyad004","DOIUrl":"10.1093/discim/kyad004","url":null,"abstract":"<p><p>The clinical success of immune checkpoint blockade in some patients has transformed treatment approaches in cancer and offers the hope of durable curative responses. Building from studies of chronic infection, the composition of tumour infiltrating lymphocytes and in particular, the spectrum of exhausted CD8 T cells has now been characterized in detail, profiling the phenotype, function, transcriptional regulation and even the epigenetic changes. However, what remains less clear is how intratumoural immune cells interface with populations in the periphery, both in terms of sustaining the response in cancer, but also in establishing systemic memory responses that can provide long-term protection. Here we will succinctly review the current understanding of the anti-tumour response, consider the tissue microenvironments that support key cellular subsets and the extent to which cellular migration between these sites impacts the response.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"2 1","pages":"kyad004"},"PeriodicalIF":0.0,"publicationDate":"2023-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10052398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9235516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Discovery immunologyPub Date : 2023-02-07eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad003
Katie J Smith, Giuseppe Sciumè, Shoba Amarnath
{"title":"Twenty-One Flavors of Type 1 Innate Lymphoid Cells with PD-1 (Programmed Cell Death-1 Receptor) Sprinkles.","authors":"Katie J Smith, Giuseppe Sciumè, Shoba Amarnath","doi":"10.1093/discim/kyad003","DOIUrl":"10.1093/discim/kyad003","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) are tissue-resident immune cells that have been recently implicated in initiating and driving anti-tumor responses. ILCs are classified into three main groups, namely type 1 ILCs (ILC1), type 2 ILCs, and type 3 ILCs. All three groups have been implicated in either eliciting pro or anti-tumor immune responses in different cancer subtypes with the consensus that ILCs cannot be overlooked within the field of anti-tumor immune responses. In this review, we will specifically expand on the knowledge on ILC1, their characterization, function, and plasticity in anti-cancer immune responses. Within this premise, we will discuss caveats of ILC1 characterization, and expand on the expression and function of immune checkpoint receptors within ILC1 subsets, specifically focusing on the role of programmed cell death-1 receptor in controlling specific ILC1 responses. We summarize that ILC1s are a vital component in initiating anti-tumor responses and can be boosted by checkpoint receptors.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":" ","pages":"kyad003"},"PeriodicalIF":0.0,"publicationDate":"2023-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49467195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Discovery immunologyPub Date : 2023-01-19eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad002
Jessica Mallaby, William Mwangi, Joseph Ng, Alexander Stewart, Daniel Dorey-Robinson, David Kipling, Uri Hershberg, Franca Fraternali, Venugopal Nair, Deborah Dunn-Walters
{"title":"Diversification of immunoglobulin genes by gene conversion in the domestic chicken (<i>Gallus gallus</i> domesticus).","authors":"Jessica Mallaby, William Mwangi, Joseph Ng, Alexander Stewart, Daniel Dorey-Robinson, David Kipling, Uri Hershberg, Franca Fraternali, Venugopal Nair, Deborah Dunn-Walters","doi":"10.1093/discim/kyad002","DOIUrl":"10.1093/discim/kyad002","url":null,"abstract":"<p><p>Sustainable modern poultry production depends on effective protection against infectious diseases and a diverse range of antibodies is key for an effective immune response. In the domestic chicken, somatic gene conversion is the dominant process in which the antibody immunoglobulin genes are diversified. Affinity maturation by somatic hypermutation (SHM) also occurs, but the relative contribution of gene conversion versus somatic hypermutation to immunoglobulin (Ig) gene diversity is poorly understood. In this study, we use high throughput long-read sequencing to study immunoglobulin diversity in multiple immune-associated tissues in Rhode Island Red chickens. To better understand the impact of genetic diversification in the chicken, a novel gene conversion identification software was developed (BrepConvert). In this study, BrepConvert enabled the identification of over 1 million gene conversion events. Mapping the occurrence of putative somatic gene conversion (SGC) events throughout the variable gene region revealed repetitive and highly restricted patterns of genetic insertions in both the antibody heavy and light chains. These patterns coincided with the locations of genetic variability in available pseudogenes and align with antigen binding sites, predominately the complementary determining regions (CDRs). We found biased usage of pseudogenes during gene conversion, as well as immunoglobulin heavy chain diversity gene (IGHD) preferences during V(D)J gene rearrangement, suggesting that antibody diversification in chickens is more focused than the genetic potential for diversity would suggest.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"1 1","pages":"kyad002"},"PeriodicalIF":0.0,"publicationDate":"2023-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41469775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Discovery immunologyPub Date : 2023-01-18eCollection Date: 2023-01-01DOI: 10.1093/discim/kyad001
Danielle J Smyth, Madeleine P J White, Chris J C Johnston, Anne-Marie Donachie, Marta Campillo Poveda, Henry J McSorley, Rick M Maizels
{"title":"Protection from T cell-dependent colitis by the helminth-derived immunomodulatory mimic of transforming growth factor-β, <i>Hp</i>-TGM.","authors":"Danielle J Smyth, Madeleine P J White, Chris J C Johnston, Anne-Marie Donachie, Marta Campillo Poveda, Henry J McSorley, Rick M Maizels","doi":"10.1093/discim/kyad001","DOIUrl":"10.1093/discim/kyad001","url":null,"abstract":"<p><p>In animal models of inflammatory colitis, pathology can be ameliorated by several intestinal helminth parasites, including the mouse nematode <i>Heligmosomoides polygyrus</i>. To identify parasite products that may exert anti-inflammatory effects <i>in vivo</i>, we tested <i>H. polygyrus</i> excretory-secretory (HES) products, as well as a recombinantly expressed parasite protein, transforming growth factor mimic (TGM), that functionally mimics the mammalian immunomodulatory cytokine TGF-β. HES and TGM showed a degree of protection in dextran sodium sulphate-induced colitis, with a reduction in inflammatory cytokines, but did not fully block the development of pathology. HES also showed little benefit in a similar acute trinitrobenzene sulphonic acid-induced model. However, in a T cell transfer-mediated model with recombination activation gene (RAG)-deficient mice, HES-reduced disease scores if administered throughout the first 2 or 4 weeks following transfer but was less effective if treatment was delayed until 14 days after T cell transfer. Recombinant TGM similarly dampened colitis in RAG-deficient recipients of effector T cells, and was effective even if introduced only once symptoms had begun to be manifest. These results are a promising indication that TGM may replicate, and even surpass, the modulatory properties of native parasite HES.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"2 1","pages":"kyad001"},"PeriodicalIF":0.0,"publicationDate":"2023-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9958376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9329589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}