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Science Immunology Mar 2019The spleen is the largest secondary lymphoid organ in the body and, as such, hosts a wide range of immunologic functions alongside its roles in hematopoiesis and red... (Review)
Review
The spleen is the largest secondary lymphoid organ in the body and, as such, hosts a wide range of immunologic functions alongside its roles in hematopoiesis and red blood cell clearance. The physical organization of the spleen allows it to filter blood of pathogens and abnormal cells and facilitate low-probability interactions between antigen-presenting cells (APCs) and cognate lymphocytes. APCs specific to the spleen regulate the T and B cell response to these antigenic targets in the blood. This review will focus on cell types, cell organization, and immunologic functions specific to the spleen and how these affect initiation of adaptive immunity to systemic blood-borne antigens. Potential differences in structure and function between mouse and human spleen will also be discussed.
Topics: Adaptive Immunity; Animals; Humans; Lymphocytes; Spleen
PubMed: 30824527
DOI: 10.1126/sciimmunol.aau6085 -
World Journal of Emergency Surgery :... 2017Spleen injuries are among the most frequent trauma-related injuries. At present, they are classified according to the anatomy of the injury. The optimal treatment... (Review)
Review
Spleen injuries are among the most frequent trauma-related injuries. At present, they are classified according to the anatomy of the injury. The optimal treatment strategy, however, should keep into consideration the hemodynamic status, the anatomic derangement, and the associated injuries. The management of splenic trauma patients aims to restore the homeostasis and the normal physiopathology especially considering the modern tools for bleeding management. Thus, the management of splenic trauma should be ultimately multidisciplinary and based on the physiology of the patient, the anatomy of the injury, and the associated lesions. Lastly, as the management of adults and children must be different, children should always be treated in dedicated pediatric trauma centers. In fact, the vast majority of pediatric patients with blunt splenic trauma can be managed non-operatively. This paper presents the World Society of Emergency Surgery (WSES) classification of splenic trauma and the management guidelines.
Topics: Abdominal Injuries; Adult; Conservative Treatment; Guidelines as Topic; Hemodynamics; Humans; Spleen; Wounds and Injuries
PubMed: 28828034
DOI: 10.1186/s13017-017-0151-4 -
Immunology Jul 2015The microanatomical structure of the spleen has been primarily described in mice and rats. This leads to terminological problems with respect to humans and their... (Review)
Review
The microanatomical structure of the spleen has been primarily described in mice and rats. This leads to terminological problems with respect to humans and their species-specific splenic microstructure. In mice, rats and humans the spleen consists of the white pulp embedded in the red pulp. In the white pulp, T and B lymphocytes form accumulations, the periarteriolar lymphatic sheaths and the follicles, located around intermediate-sized arterial vessels, the central arteries. The red pulp is a reticular connective tissue containing all types of blood cells. The spleen of mice and rats exhibits an additional well-delineated B-cell compartment, the marginal zone, between white and red pulp. This area is, however, absent in human spleen. Human splenic secondary follicles comprise three zones: a germinal centre, a mantle zone and a superficial zone. In humans, arterioles and sheathed capillaries in the red pulp are surrounded by lymphocytes, especially by B cells. Human sheathed capillaries are related to the splenic ellipsoids of most other vertebrates. Such vessels are lacking in rats or mice, which form an evolutionary exception. Capillary sheaths are composed of endothelial cells, pericytes, special stromal sheath cells, macrophages and B lymphocytes. Human spleens most probably host a totally open circulation system, as connections from capillaries to sinuses were not found in the red pulp. Three stromal cell types of different phenotype and location occur in the human white pulp. Splenic white and red pulp structure is reviewed in rats, mice and humans to encourage further investigations on lymphocyte recirculation through the spleen.
Topics: Anatomy, Comparative; Animals; B-Lymphocytes; Capillaries; Cell Movement; Humans; Mice; Models, Anatomic; Rats; Spleen
PubMed: 25827019
DOI: 10.1111/imm.12469 -
Cell Aug 2018A highly multiplexed cytometric imaging approach, termed co-detection by indexing (CODEX), is used here to create multiplexed datasets of normal and lupus (MRL/lpr)...
A highly multiplexed cytometric imaging approach, termed co-detection by indexing (CODEX), is used here to create multiplexed datasets of normal and lupus (MRL/lpr) murine spleens. CODEX iteratively visualizes antibody binding events using DNA barcodes, fluorescent dNTP analogs, and an in situ polymerization-based indexing procedure. An algorithmic pipeline for single-cell antigen quantification in tightly packed tissues was developed and used to overlay well-known morphological features with de novo characterization of lymphoid tissue architecture at a single-cell and cellular neighborhood levels. We observed an unexpected, profound impact of the cellular neighborhood on the expression of protein receptors on immune cells. By comparing normal murine spleen to spleens from animals with systemic autoimmune disease (MRL/lpr), extensive and previously uncharacterized splenic cell-interaction dynamics in the healthy versus diseased state was observed. The fidelity of multiplexed spatial cytometry demonstrated here allows for quantitative systemic characterization of tissue architecture in normal and clinically aberrant samples.
Topics: Animals; Antibodies; Disease Models, Animal; Female; Image Processing, Computer-Assisted; Lupus Erythematosus, Systemic; Male; Mass Spectrometry; Mice; Mice, Inbred MRL lpr; Oligonucleotide Probes; Spleen
PubMed: 30078711
DOI: 10.1016/j.cell.2018.07.010 -
Hepatology (Baltimore, Md.) May 2023Monocyte-derived macrophages (MoMFs), a dominant population of hepatic macrophages under inflammation, play a crucial role in liver fibrosis progression. The spleen...
BACKGROUND AND AIMS
Monocyte-derived macrophages (MoMFs), a dominant population of hepatic macrophages under inflammation, play a crucial role in liver fibrosis progression. The spleen serves as an extra monocyte reservoir in inflammatory conditions; however, the precise mechanisms of involvement of the spleen in the pathogenesis of liver fibrosis remain unclear.
APPROACH AND RESULTS
By splenectomy and splenocyte transfusion, it was observed that splenic CD11b + cells accumulated intrahepatically as Ly6C lo MoMFs to exacerbate CCl 4 -induced liver fibrosis. The splenocyte migration into the fibrotic liver was further directly visualized by spleen-specific photoconversion with KikGR mice and confirmed by CD45.1 + /CD45.2 + spleen transplantation. Spleen-derived CD11b + cells purified from fibrotic livers were then annotated by single-cell RNA sequencing, and a subtype of CD11b + CD43 hi Ly6C lo splenic monocytes (sM-1s) was identified, which was markedly expanded in both spleens and livers of mice with liver fibrosis. sM-1s exhibited mature feature with high expressions of F4/80, produced much ROS, and manifested preferential migration into livers. Once recruited, sM-1s underwent sequential transformation to sM-2s (highly expressed Mif , Msr1 , Clec4d , and Cstb ) and then to spleen-derived macrophages (sMφs) with macrophage features of higher expressions of CX 3 CR1, F4/80, MHC class II, and CD64 in the fibrotic hepatic milieu. Furthermore, sM-2s and sMφs were demonstrated capable of activating hepatic stellate cells and thus exacerbating liver fibrosis.
CONCLUSIONS
CD11b + CD43 hi Ly6C lo splenic monocytes migrate into the liver and shift to macrophages, which account for the exacerbation of liver fibrosis. These findings reveal precise mechanisms of spleen-liver axis in hepatic pathogenesis and shed light on the potential of sM-1 as candidate target for controlling liver diseases.
Topics: Mice; Animals; Spleen; Macrophages; Liver; Liver Cirrhosis; Monocytes; Mice, Inbred C57BL
PubMed: 36098707
DOI: 10.1002/hep.32782 -
International Immunology Feb 2019Tissue-resident macrophages in the spleen, including red pulp and white pulp macrophages, marginal zone macrophages (MZMs) and marginal zone metallophilic macrophages...
Tissue-resident macrophages in the spleen, including red pulp and white pulp macrophages, marginal zone macrophages (MZMs) and marginal zone metallophilic macrophages (MMMs), are highly heterogeneous as a consequence of adaptation to tissue-specific environments. Each macrophage sub-population in the spleen is usually identified based on the localization, morphology and membrane antigen expression by immunohistochemistry. However, their phenotypical and functional characteristics remain incompletely understood due to the difficulty of identification and isolation by flow cytometry. We used a cocktail of three enzymes (Collagenase D, Dispase I and DNase I), rather than traditional mechanical grinding, for isolation of each sub-population, which resulted in significant improvement of isolation of these macrophage sub-populations, particularly MZMs and MMMs, as determined by CD11bhiF4/80medTim4hi and CD11bhiF4/80medTim4med, respectively. This method should be helpful for molecular and functional characterization of each splenic resident macrophage sub-population.
Topics: Animals; Biomarkers; Cell Separation; Flow Cytometry; Immunohistochemistry; Immunophenotyping; Macrophages; Mice; Phagocytosis; Spleen
PubMed: 30256964
DOI: 10.1093/intimm/dxy064 -
The Indian Journal of Medical Research Apr 2019
Topics: Burkholderia pseudomallei; Female; Gram-Negative Bacteria; Humans; Liver; Magnetic Resonance Imaging; Melioidosis; Spleen; Young Adult
PubMed: 31411183
DOI: 10.4103/ijmr.IJMR_2018_17 -
Current Oncology (Toronto, Ont.) Nov 2021Primary splenic lymphoma (PSL) is a rare malignancy representing about 1% of all lymphoproliferative disorders, when using a strict definition that allows only... (Review)
Review
Primary splenic lymphoma (PSL) is a rare malignancy representing about 1% of all lymphoproliferative disorders, when using a strict definition that allows only involvement of spleen and hilar lymph nodes. In contrast, secondary low-grade B-cell lymphomas in the spleen, such as follicular lymphomas (FL), lymphoplasmacytic lymphoma and chronic lymphocytic leukemia/ small lymphocytic lymphoma, particularly as part of advanced stage disease, are more common. Indolent B cell lymphomas expressing CD10 almost always represent FL, which in its primary splenic form is the focus of this review. Primary splenic follicular lymphoma (PSFL) is exceedingly infrequent. This type of lymphoproliferative disorder is understudied and, in most cases, clinically characterized by splenomegaly or cytopenias related to hypersplenism. The diagnosis requires correlation of histopathology of spleen, blood and/or bone marrow with the correct immunophenotype (determined by flow cytometry and/or immunohistochemistry) and if necessary, additional molecular profiling. Management of this incurable disease is evolving, and splenectomy remains the mainstream treatment for stage I PSFL.
Topics: Humans; Immunohistochemistry; Immunophenotyping; Lymphoma, B-Cell; Lymphoma, Follicular; Spleen
PubMed: 34898578
DOI: 10.3390/curroncol28060407 -
Cellular Immunology Aug 2018Macrophage heterogeneity in the spleen has been long documented, with four subsets populating the different splenic compartments. The diverse environments on the splenic... (Review)
Review
Macrophage heterogeneity in the spleen has been long documented, with four subsets populating the different splenic compartments. The diverse environments on the splenic compartments determine their varied phenotype and functions. In the white pulp, highly phagocytic macrophages contribute to the generation of the immune response. The marginal zone contains two populations of macrophages, which also contribute to the immune response. Their strategic position in the bloodstream and their unique phenotype confer them a crucial role in the defense against blood borne pathogens, placing them at the crossroad between innate and adaptive immune responses. Macrophages in the red pulp are classically linked to homeostatic and metabolic functions in erythrocyte phagocytosis and iron recycling. We review here recent advances demonstrating the importance of macrophage ontogeny and organ development in determining the phenotype, transcriptional profile and, ultimately, the functions of the populations of splenic macrophages.
Topics: Adaptive Immunity; Animals; Energy Metabolism; Erythrocytes; Homeostasis; Humans; Immunity, Innate; Macrophages; Phagocytosis; Spleen
PubMed: 29779612
DOI: 10.1016/j.cellimm.2018.05.005 -
Frontiers in Cellular and Infection... 2018The spleen is a secondary lymphoid organ responsible for immune surveillance against blood-circulating pathogens. Absence of the spleen is associated with increased... (Review)
Review
The spleen is a secondary lymphoid organ responsible for immune surveillance against blood-circulating pathogens. Absence of the spleen is associated with increased susceptibility to systemic spread and fatal infection by different pathogens. Severe forms of visceral leishmaniasis are associated with disorganization of spleen compartments where cell interactions essential for splenic immunological function take place. White pulp atrophies, secondary lymphoid follicles and marginal zones vanish, and the boundaries separating white and red pulp blur. Leukocyte populations are reduced or disappear or are replaced by plasma cells. In this paper, we review the published data on spleen disorganization in severe forms of visceral leishmaniasis and propose a histological classification to help the exchange of information among research groups.
Topics: Animals; Chronic Disease; Humans; Leishmania infantum; Leishmaniasis, Visceral; Leukocytes; Spleen
PubMed: 30483481
DOI: 10.3389/fcimb.2018.00394