Islet resident macrophages are the predominant myeloid cell of the pancreatic islets of langerhans.[1]
| Pancreatic Islet Macrophage | |
|---|---|
 Immunohistochemistry for a pancreatic islet (white) with macrophages (green and red), and cell nuclei (blue) | |
| Details | |
| Precursor | Hematopoietic Stem Cell |
| System | Immune system |
| Location | Pancreatic islet |
| Identifiers | |
| Latin | pancreaticae insulae macrophagocytus |
| TH | H2.00.01.0.00005 |
| Anatomical terms of microanatomy | |
Structure edit
Markers edit
Islet resident macrophages are uniquely found within the endocrine tissue (islet), while nearby in the nearby acinar tissue, macrophages express a different repertoire of CD (cluster of differentiation) markers and come from a different developmental origin. In terms of expression markers, islet macrophages are positive for; F4/80, CD11b, CD11c, MHC-II, CD64, CD68, LyzM (lysozyme), Cx3cr1 and are negative for; CD206 (mannose receptor), CD301, CD103.
Development edit
The mesoderm gives rise to myeloid progenitor cells, which further differentiate into macrophage populations.[2] As opposed to macrophages in the islet stroma (tissue), whose developmental origin is from the yolk sac (primitive hematopoiesis), islet resident progenitors come from hematopoietic stem cells (HSCs) of the definitive hematopoiesis. These cells are seen in fetal liver during mid-gestation E10-E11,[3] and are thought to colonize the bone marrow during late gestation E15.[4] As a unique population in terms of developmental origin, these resident macrophages have a unique phenotype in which they are long lived, self-renew locally, and stay confined within the islet parenchyma.
Function edit
Islet resident macrophages depend on the expression of colony stimulating factor (CSF1). Knockout mice for the CSF-1 gene cause islets to be devoid of resident macrophages. These mice show a reduced beta cell mass as well as developmental defects.[5] This as well as other observations, showing that islet resident macrophages promote beta cell proliferation suggest that islet macrophages are likely important contributors to the function of the pancreatic islet.[6][7] In contrast to the possible supportive role within the islet, these specialized macrophages are also required for the initiation of the adaptive immune response during type 1 diabetes (T1D) in mice. They do this by presenting beta cell derived peptides using MHC II receptors to T-cells in the islet.[8] Once activated, T-cells stimulate the adaptive immune system, which leads to the destruction of pancreatic islets due to an autoimmune response.
History edit
The islet resident macrophage was first identified in 1979 as an antigen-presenting cell (APC),[9] which expresses major histocompatibility complexes (MHCs). Later in 1984 this APC was further classified by using a macrophage specific marker F4/80.[10] In 1988 it was discovered that macrophages play an essential role in the progression of insulin dependent diabetes mellitus (T1D), in an animal model for non-obese diabetes (NOD mice). The role of pancreatic macrophages were later shown to play an important role in type 2 diabetes as well, by contributing to islet inflammation.[11] The origin and turnover in the normal state was characterized by Emil Unanue in 2015.
See also edit
References edit
- ^ Calderon, B (2016). "The pancreas anatomy conditions the origin and properties of resident macrophages". J Exp Med. 212 (9): 1497–1512. doi:10.1084/jem.20150496. PMC 4577842. PMID 26347472.
- ^ Hsu, K (2001). "Zebrafish myelopoiesis and blood cell development". Curr Opin Hematol. 8 (4): 245–51. doi:10.1097/00062752-200107000-00011. PMID 11561163. S2CID 45421423.
- ^ Dzierzak, E (1995). "Mouse embryonic hematopoiesis". Trends Genet. 11 (9): 359–66. doi:10.1016/S0168-9525(00)89107-6. PMID 7482788.
- ^ Byrd, N (2002). "Hedgehog is required for murine yolk sac angiogenesis". Development. 129 (2): 361–72. doi:10.1242/dev.129.2.361. PMID 11807029.
- ^ Banaei-Bouchareb, L (2004). "Insulin mass is altered in Csf1op/Csf1op macrophage-deficient mice". J Leukoc Biol. 76 (2): 359–67. doi:10.1189/jlb.1103591. PMID 15178709. S2CID 23700442.
- ^ Brissova, M (2014). "Islet microenvironment, modulated by vascular endothelial growth growth factor-A signaling promotes B cell regeneration". Cell Metab. 19 (3): 498–511. doi:10.1016/j.cmet.2014.02.001. PMC 4012856. PMID 24561261.
- ^ Tessem, Jeffery S.; Jensen, Jan N.; Pelli, Hanna; Dai, Xu-Ming; Zong, Xiao-Hua; Stanley, E. Richard; Jensen, Jan; DeGregori, James (2008). "Critical roles for macrophages in islet angiogenesis and maintenance during pancreatic degeneration". Diabetes. 57 (6): 1605–1617. doi:10.2337/db07-1577. PMC 2575065. PMID 18375440.
- ^ Calderon, B (2014). "The Central Role of Antigen Presentation in Islets of Langerhans in Autoimmune Diabetes". Curr Opin Immunol. 26 (26): 32–40. doi:10.1016/j.coi.2013.10.011. PMC 4118295. PMID 24556398.
- ^ Lacy, PE (1979). "Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injects of ALS". Science. 204 (4390): 312–3. Bibcode:1979Sci...204..312L. doi:10.1126/science.107588. PMID 107588.
- ^ Hume, DA (1984). "The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of endocrine organs". Proc Natl Acad Sci USA. 81 (13): 4174–7. Bibcode:1984PNAS...81.4174H. doi:10.1073/pnas.81.13.4174. PMC 345391. PMID 6377311.
- ^ Xiao, X (2015). "Concise Review: New Insights Into the Role of Macrophages in B-cell Proliferation". Stem Cells Transl Med. 4 (6): 655–658. doi:10.5966/sctm.2014-0248. PMC 4449096. PMID 25900729.