title: αB-Crystallin regulates expansion of CD11b⁺Gr-1⁺ immature myeloid cells during tumor progression.
abstract: 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.
authors.affiliation: Department of Immunology, Genetics, and Pathology, The Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Lothar C
authors.initials: LC
authors.lastname: Dieterich
authors.forename: Petter
authors.initials: P
authors.lastname: Schiller
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
authors.forename: Eric F
authors.initials: EF
authors.lastname: Wawrousek
authors.forename: Angelica
authors.initials: A
authors.lastname: Loskog
authors.forename: Alkwin
authors.initials: A
authors.lastname: Wanders
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.forename: Anna
authors.initials: A
authors.lastname: Dimberg
mesh_terms: D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000276:immunology*; D039481:CD11b Antigen / Q000276:immunology*; D002454:Cell Differentiation; D003459:Crystallins / Q000502:physiology*; D017931:DNA Primers; D018450:Disease Progression; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018243:Teratocarcinoma / Q000276:immunology / Q000473:pathology*
chemical_list: D039481:CD11b Antigen; D003459:Crystallins; D017931:DNA Primers; C509295:ITGAM protein, human