Liver-spleen axis: Intersection between immunity, infections and metabolism

Table 1 Function of the spleen

Red pulp

Extramedullary hematopoiesis if required

Facilitating an environment wherein erythrocytes rid themselves of solid waste material

Blood filter for foreign material and damaged and senescent blood cells

Storage site for iron, erythrocytes, platelets, plasmablasts and plasma cells

Rapid release of antigen-specific antibodies into the circulation produced by red pulp plasma cells Defense against bacteria using iron metabolism by its macrophages

White pulp

T cell zone (periarterial lymphatic sheath) and B cell zone (follicles)

Storage site for B and T lymphocytes

Development of B and T lymphocytes upon antigenic challenge

Release of immunoglobulins upon antigenic challenge by B lymphocytes

Production of immune mediators involved in clearance of bacteria such as complement, opsonins, properdin and tuftsin

Marginal zone

Phagocytosis of circulating microorganisms and immune complexes by MZ macrophages

Development of marginal zone B lymphocytes upon TI-2 antigenic challenge

Blood trafficking of B and T lymphocytes

Release of immunoglobulins upon antigenic challenge by splenic B lymphocytes

Table 2 Main topics

Congenital asplenia in humans

There are two types of congenital asplenia: with or without other clinically evident abnormalities

Tcf21, Bapx1, Pbx1 and Tlx1 are crucial for spleen development

The molecular mechanisms and the etiology of spleen development are still unknown

How the anatomical and histological composition of the spleen can guarantee its function?

The phagocytosis of old and damaged cells, particles and blood-borne microorganisms from local macrophages takes place in the red pulp

The spleen is fundamental in the recycling of iron

Exercise in splenectomized individuals can decrease splanchnic flow and increase blood viscosity

Most important differences between mice and humans in the spleen organization and functionality are revealed in the immune response

Role of spleen in limiting bacterial infection

Splenectomized and asplenic patients are more susceptible to infections, especially caused by Haemophilus influenzae

Subjects with functional asplenia develope the same type of infections

The spleen and natural antibodies

B cells may be divided in two main subpopulations on the basis of life development (fetal or adult), superficie markers and functions

Spleen might be central to the generation or survival of the B-1a population and therefore splenectomy would lead to their depletion

Other functions of the spleen

There is a probable relationship among GALT and spleen in humans

The spleen also has important hematological functions

In the spleen were found stem cells with several differentiation properties: haematological, osteogenic and maybe pancreatic

Assessment of spleen function

Hematologycal and immunological parameters should be used in the assessment of spleen function

The best approach to gauge all the facets of the splenic function is the radioisotope method

Spleen as a new player

There is an association between spleen enlargement and NAFLD

SLD could be used as new marker for assessing splenic function

Initial data have shown that SLD is more sensitive than IL-6 and VEGF in discriminating NASH from FL, and the optimal cut-off value for SLD is 116 mm

Infections tendency in obesity and the possible link with the spleen

Obese subjects have an increased risk to develop malignancies and infections

The pathophysiological mechanisms by which cellular immune functions are affected by obesity are still under investigation but the spleen may have an important role

GALT: Gut-associated lymphoid tissue; NAFLD: Nonalcoholic fatty liver disease; SLD: Spleen longitudinal diameter; VEGF: Vascular endothelial growth factor; IL-6: Interleukin-6; NASH: Nonalcoholic steatohepatitis.