Altered eosinophil profile in mice with ST6Gal-1 deficiency: An additional role for ST6Gal-1 generated by the P1 promoter in regulating allergic inflammation

Mehrab Nasirikenari, E. V. Chandrasekaran, Khushi L. Matta, Brahm H. Segal, Paul N. Bogner, Amit A. Lugade, Yasmin Thanavala, James J. Lee, Joseph T.Y. Lau

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Cumulative evidence indicates that the sialyltransferase ST6Gal-1 and the sialyl-glycans, which it constructs, are functionally pleiotropic. Expression of the ST6Gal-1 gene is mediated by six distinct promoter/regulatory regions, and we hypothesized that these promoters may be used differentially to produce ST6Gal-1 for different biologic purposes. To examine this hypothesis, we compared a mouse with a complete deficiency in ST6Gal-1 (Siat1 null) with another mouse that we have created previously with a disruption only in the P1 promoter (Siat1ΔP1). We noted previously greater neutrophilic inflammation associated with ST6Gal-1 deficiency. Here, we report that ST6Gal-1-deficient mice also have significantly elevated eosinophilic responses. Upon i.p. thioglycollate elicitation, eosinophils accounted for over 20% of the total peritoneal inflammatory cell pool in ST6Gal-1-deficient animals, which was threefold greater than in corresponding wild-type animals. A principal feature of allergic respiratory inflammation is pulmonary eosinophilia, we evaluated the role of ST6Gal-1 in allergic lung inflammation. Using OVA and ABPA experimental models of allergic airways, we showed that ST6Gal-1 deficiency led to greater airway inflammation characterized by excessive airway eosinophilia. The severity of airway inflammation was similar between Siat1ΔP1 and Siat1 null mice, indicating a role for P1-generated ST6Gal-1 in regulating eosinophilic inflammation. Colony-forming assays suggested greater IL-5-dependent eosinophil progenitor numbers in the marrow of ST6Gal-1-deficient animals. Moreover, allergen provocation of wild-type mice led to a significant reduction in P1-mediated ST6Gal-1 mRNA and accompanied decline in circulatory ST6Gal-1 levels. Taken together, the data implicate ST6Gal-1 as a participant in regulating not only Th1 but also Th2 responses, and ST6Gal-1 deficiency can lead to the development of more severe allergic inflammation with excessive eosinophil production.

Original languageEnglish (US)
Pages (from-to)457-466
Number of pages10
JournalJournal of Leukocyte Biology
Issue number3
StatePublished - Mar 2010


  • Allergic airway
  • Myelopoiesis
  • Sialic acid
  • Sialyltransferase
  • Th2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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