alphaB-Crystallin regulates expansion of CD11b(+)Gr-1(+) immature myeloid cells during tumor progression
2013 (English)In: FASEB J, Vol. 27, no 1, 151-62 p.Article in journal (Refereed) Published
The molecular chaperone alphaB-crystallin has emerged as a target for cancer therapy due to its expression in human tumors and its role in regulating tumor angiogenesis. alphaB-crystallin also reduces neuroinflammation, but its role in other inflammatory conditions has not been investigated. Here, we examined whether alphaB-crystallin regulates inflammation associated with tumors and ischemia. We found that CD45(+) leukocyte infiltration is 3-fold increased in tumors and ischemic myocardium in alphaB-crystallin-deficient mice. Notably, alphaB-crystallin is prominently expressed in CD11b(+) Gr-1(+) immature myeloid cells (IMCs), known as regulators of angiogenesis and immune responses, while lymphocytes and mature granulocytes show low alphaB-crystallin expression. alphaB-Crystallin deficiency results in a 3-fold higher accumulation of CD11b(+) Gr-1(+) IMCs in tumors and a significant rise in CD11b(+) Gr-1(+) IMCs in spleen and bone marrow. Similarly, we noted a 2-fold increase in CD11b(+) Gr-1(+) IMCs in chronically inflamed livers in alphaB-crystallin-deficient mice. The effect of alphaB-crystallin on IMC accumulation is limited to pathological conditions, as CD11b(+) Gr-1(+) IMCs are not elevated in naive mice. Through ex vivo differentiation of CD11b(+) Gr-1(+) cells, we provide evidence that alphaB-crystallin regulates systemic expansion of IMCs through a cell-intrinsic mechanism. Our study suggests a key role of alphaB-crystallin in limiting expansion of CD11b(+) Gr-1(+) IMCs in diverse pathological conditions.
Place, publisher, year, edition, pages
2013. Vol. 27, no 1, 151-62 p.
Animals, Antigens, CD11b/*immunology, Base Sequence, Bone Marrow Cells/*immunology, Cell Differentiation, Crystallins/*physiology, DNA Primers, Disease Progression, Humans, Mice, Mice, Inbred C57BL, Teratocarcinoma/immunology/*pathology
IdentifiersURN: urn:nbn:se:umu:diva-110902ISBN: 1530-6860 (Electronic) 0892-6638 (Linking)OAI: oai:DiVA.org:umu-110902DiVA: diva2:865888
Dieterich, Lothar C Schiller, Petter Huang, Hua Wawrousek, Eric F Loskog, Angelica Wanders, Alkwin Moons, Lieve Dimberg, Anna eng 2012/10/04 06:00 FASEB J. 2013 Jan;27(1):151-62. doi: 10.1096/fj.12-213017. Epub 2012 Oct 2.2015-10-292015-10-292015-10-29