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Regulation of Allergic Inflammation and Eosinophil Recruitment in Mice
Lacking the Transcription Factor NFAT1: Role of Interleukin-4 (IL-4)
and IL-5
João P.B. Viola,
Alexander Kiani,
Patricia T. Bozza, and
Anjana Rao
From the Center for Blood Research and the Department of Pathology,
Harvard Medical School, Boston, MA; and Departamento de Fisiologia e
Farmacodinâmica, Fundação Oswaldo Cruz, Rio de
Janeiro, RJ, Brazil.
Transcription factors of the NFAT (nuclear factor of activated T
cells) family regulate the expression of many genes encoding immunoregulatory cytokines and cell surface proteins during the immune
response. The NFAT protein NFAT1 (NFATp) is expressed and functional in
T cells, B cells, mast cells, and natural killer cells. Here we report
a detailed analysis of the enhanced eosinophil responses of
NFAT1-deficient mice, observed in an in vivo model of allergic
inflammation. In addition to the pleural eosinophilia described
previously, NFAT1 / mice that have been sensitized
with antigen display a significant increase, relative to wild-type
mice, in the numbers of eosinophils in bone marrow and peripheral
blood. After restimulation with antigen in vitro, antigen-responsive T
cells from the draining lymph nodes of NFAT1/ mice
show increased expression of mRNA encoding the Th2 cytokines interleukin-4 (IL-4), IL-5, and IL-13. Consistent with this finding, there is a pronounced increase in the levels of IL-5 and IL-13 in the
pleural cavities of sensitized NFAT1/ mice after
allergen challenge in vivo. Furthermore, development of eosinophilia
depends on overexpression of IL-4 and IL-5, because it is strongly
inhibited by administration of neutralizing antibodies to either of
these cytokines. These results indicate that NFAT1-deficient mice are
prone to develop a classically allergic phenotype characterized by
eosinophilia and increased production of Th2 cytokines. Thus, the
presence of NFAT1 might inhibit the allergic response, perhaps by
interfering with the development of Th2 immune responses, and the lack
or dysfunction of NFAT1 could potentially underlie certain cases of
atopic disease.
Blood, Vol. 91 No. 7 (April 1), 1998:
pp. 2223-2230
© 1998 by The American Society of Hematology.
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