?B-Crystallin regulates expansion of CD11b?Gr-1? immature myeloid cells during tumor progression.

ABSTRACT: The molecular chaperone ?B-crystallin has emerged as a target for cancer therapy due to its expression in human tumors and its role in regulating tumor angiogenesis. ?B-crystallin also reduces neuroinflammation, but its role in other inflammatory conditions has not been investigated. Here, we examined whether ?B-crystallin regulates inflammation associated with tumors and ischemia. We found that CD45(+) leukocyte infiltration is 3-fold increased in tumors and ischemic myocardium in ?B-crystallin-deficient mice. Notably, ?B-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 ?B-crystallin expression. ?B-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 ?B-crystallin-deficient mice. The effect of ?B-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 ?B-crystallin regulates systemic expansion of IMCs through a cell-intrinsic mechanism. Our study suggests a key role of ?B-crystallin in limiting expansion of CD11b(+) Gr-1(+) IMCs in diverse pathological conditions.

SUBMITTER: Dieterich LC 

PROVIDER: S-EPMC3528311 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature