Spleen: A new role for an old player? (original) (raw)
Related papers
Liver-spleen axis: Intersection between immunity, infections and metabolism
World Journal of Gastroenterology, 2013
Spleen has been considered a neglected organ so far, even though is strictly linked to liver. The spleen plays an important role in the modulation of the immune system and in the maintenance of peripheral tolerance via the clearance of circulating apoptotic cells, the differentiation and activation of T and B cells and production of antibodies in the white pulp. Moreover, splenic macrophages are able to remove bacteria from the blood and protect from sepsis during systemic infections. We review the spleen function and its assessment in humans starting from the description of spleen diseases, ranging from the congenital asplenia to secondary hyposplenism. From the literature data it is clear that obesity in humans affects different compartments of immune system, even thought there are still few data available on the implicated mechamisms. The intent is to enable clinicians to evaluate the newly recognized role of metabolic and endocrine functions of the spleen with special emphasis to obesity and nonalcoholic fatty liver disease in the context of the available literature. Moreover, understanding the spleen function could be important to develop appropriate prevention strategies in order to counteract the pandemia of obesity. In this direction, we suggest spleen longitudinal diameter at ultrasonography, as simple, cheap and largely available tool, be used as new marker for assessing splenic function, in the context of the so-called liver-spleen axis.
Functions of Spleen in Health and Disease
2015
Spleen is a capsulated and compartmentalized lympho id organ with a complex vascular and cellular organization. It develops from dorsal mesogastrium. The spleen pe rforms a number of physiological functions namely, phagocytosis of aging erythrocytes and platelets, recycling iron, inducing immune response against blood antige s, and defending against invading bacteria, fungi, viruses, prions and otherinfective agents. Because thespleen has only the efferent lymphatic vessels, it is therefore, involv ed in the filtration of blood but not lymph. The splenic functions can be affected by immune sup pressant drugs, vaccines and biological products, chemoand radiation-therapy, resulting i splenomegaly and thrombocytopenia (reduced number of platelets). Recently, it has be en shown that the splenic monocytes play a significant role in the regeneration of heart tissu e following a heart attack.
The spleen in liver cirrhosis: revisiting an old enemy with novel targets
Journal of translational medicine, 2017
The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension. These splenic abnormalities correlate with and have been postulated to facilitate the progression of liver fibrosis to cirrhosis, although precise mechanisms remain poorly understood. In this review, we summarize the literature to highlight the mechanistic contributions of splenomegaly and hypersplenism to the development of liver cirrhosis, focusing on three key aspects: hepatic fibrogenesis, hepatic immune microenvironment dysregulation and liver regeneration. We conclude with a discussion of the possible therapeutic strategies for modulating splenic abnormalities, including the novel potential usage of nanomedicine in non-surgically targetting splenic disorders for the treatment of liver cirrhosis.
Spleen in innate and adaptive immunity regulation
AIMS Allergy and Immunology
The spleen is a large secondary lymphoid organ located in the bloodstream , primarily functioning as a massive blood filter. It filtered effete red blood cells, antigen-antibody complexes, apoptotic bodies, damaged cells, among others. Spleen's myriad microanatomy reflects the diversity and complexity of its functions. As a specialized immune organ, the spleen immune system plays a significant role in innate and adaptive immunity. Specialized innate immune cells like B cells, natural killer (NK) cells, and macrophages populate locations within the spleen. Specifically, the spleen is a crucial organ for peripheral immune tolerance, complementing central immune tolerance. Spleen remains the only organ in the body capable of mounting an appropriate immune response to encapsulated bacteria. Spleen houses tolerogenic immune cells like CD8 + Treg cells, F4/80 + macrophages, CD68 + F4/80 + red pulp macrophages, CD169 + metallophillic macrophages, CD8 + CD205 + splenic dendritic cells (DCs), splenic CD8α + CD103 + CD207 + DCs, CD43 +ve CD19 hi CD5 +ve IgM hi IgD lo B cells, and splenic NKT cells that express regulated on activation normal T cell expressed and secreted (RANTES/CCL5) chemokine. Splenocytes are extra-thymic autoimmune regulator gene (AIRE) expressing cells that regulate tissue-specific antigens' expression to confer peripheral immune tolerance. As such, the spleen provides the right site for counteracting autoimmunity. Splenectomy in both study animals and humans results in overwhelming infections with, especially encapsulated bacteria. The anterior chamber-associated immune deviation (ACAID) is closely related to the spleen that needs to be studied to improve transplant survival. The role of the spleen in anti-tumor immunity yields an inconclusive result. In-depth research is needed to find which cells or pathways are linked to favorable outcomes concerning cancer. Understanding the spleen's microanatomy and physiology will provide a 2
Immunophenotypic analysis of human spleen compartments
Annals of Anatomy - Anatomischer Anzeiger, 2002
Microanatomical compartments of the human spleen are yet under evaluation as most of the present information comes from experiments on animals with different anatomical structures. Immune staining of stromal and blood-born cells by cell surface antigens facilitates the differentiation of functional microanatomical compartmentalization of immune organs, including the spleen. Twenty-two specimens from healthy adult subjects with the average age of 35.6+ 13.8 (Range 17 to 58) years were included in this study. Monoclonal antibodies used in this study were supplied from the 5 th, 6 th and 7 th International Workshops and Conferences on Human Leukocyte Differentiation Antigens. Tetraspan antigens presented a rather unique staining pattern in the human spleen, suggesting special roles for each (CD9, CD53, CD63, CD151 and CD231) in certain locations. Sinus lining cells presented a distinctive antigenic profile, sharing both endothelial cell (CD31, CD36, CD54, CD62R CD102, CD105, CD106 and CD146) and macrophage lineage characteristics. The sheathed capillaries were not restricted to the perifollicular zone alone. Extracellular matrix receptors (CD49 a, CD49 b, CD49 c, CD49 e, CD49f, CD29 and CD44) stained the penicillary arterioles and vascular smooth muscle. These molecules were also found on the vascular endothelium. Leukocyte antigens (CD11a, CD11b, CD22, CD43, CD45, CD45RB, CD45RO and CD50) were mainly expressed in the white and red pulp of the spleen at different intensities, excluding the penicillary arterioles. Activation antigens (CD26, CD71 and CD98) presented a diffuse and broad staining pattern. In conclusion, microanatomical compartmentalization, microcirculation and function of the human spleen were evaluated using a wide panel of monoclonal antibodies.
Biomedicines
Autoimmune hepatitis (AIH) is detected at a late stage in the course of the disease. Therefore, induction and etiology are largely unclear. It is controversial if the induction of autoimmunity occurs in the liver or in the spleen. In our experimental murine AIH model, the induction of autoimmunity did not occur in the spleen. Instead, a protective role of the spleen could be more likely. Therefore, we splenectomized mice followed by induction of experimental murine AIH. Splenectomized mice presented more severe portal inflammation. Furthermore, these mice had more IL-17, IL-23 receptor (IL-23R) and caspase 3 (casp3) and a decreased amount of erythropoietin in serum, while intrahepatic T cell compartments were unaffected. These results indicate that the spleen is not necessary for induction of AIH, and splenectomy disrupts the ability to immune regulate the intensity of hepatic inflammation, production of IL-17 and apoptosis.
Cellular Physiology and Biochemistry
Background/Aims: Liver fibrosis is a complex process of tissue remodeling in response to injury. Hepatic macrophages have been identified as a key player in this process. As the largest lymphoid organ in the body, the spleen exerts both local and systemic effects on immune cell response. Splenectomy can improve hepatic function during the treatment of liver cirrhosis. However, whether the spleen influences disease progression through the modulation of hepatic macrophages remains unclear. Methods: We examined ex vivo hepatic macrophage responses from splenectomized or sham operated rats and performed splenocyte adoptive transfer studies, in combination with in vivo CCL2 blockade, in splenectomized or sham operated rats. Results: We found that splenectomy reduced fibrosis severity and monocyte/ macrophage infiltration within the injured liver. Splenectomy also reduced secretion of the monocyte chemokine CCL2 by hepatic macrophages. Ex vivo, splenocytes, especially splenic macrophages,...