alpha B-Crystallin regulates expansion of CD11b(+)Gr-1(+) immature myeloid cells during tumor progression
2013 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 27, no 1, 151-162 p.Article in journal (Refereed) Published
The molecular chaperone αB-crystallin has emerged as a target for cancer therapy due to its expression in human tumors and its role in regulating tumor angiogenesis. αB-crystallin also reduces neuroinflammation, but its role in other inflammatory conditions has not been investigated. Here, we examined whether αB-crystallin regulates inflammation associated with tumors and ischemia. We found that CD45+ leukocyte infiltration is 3-fold increased in tumors and ischemic myocardium in αB-crystallin-deficient mice. Notably, αB-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 αB-crystallin expression. αB-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 αB-crystallin-deficient mice. The effect of αB-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 αB-crystallin regulates systemic expansion of IMCs through a cell-intrinsic mechanism. Our study suggests a key role of αB-crystallin in limiting expansion of CD11b+ Gr-1+ IMCs in diverse pathological conditions.—Dieterich, L. C., Schiller, P., Huang, H., Wawrousek, E. F., Loskog, A., Wanders, A., Moons, L., Dimberg, A. αB-Crystallin regulates expansion of CD11b+Gr-1+ immature myeloid cells during tumor progression.
Place, publisher, year, edition, pages
2013. Vol. 27, no 1, 151-162 p.
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-187588DOI: 10.1096/fj.12-213017ISI: 000313103200015PubMedID: 23033322OAI: oai:DiVA.org:uu-187588DiVA: diva2:575236