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Expression of IL-10-Triggered STAT3-Dependent IL-4Ra is Required for Induction of Arginase 1 in Visceral Leishmaniasis

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Title Expression of IL-10-Triggered STAT3-Dependent IL-4Ra
is Required for Induction of Arginase 1 in Visceral
Leishmaniasis
 
Creator Biswas, Arunima
Bhattacharya, Arijit
Kar, Susanta
Das, Pijush K
 
Subject Infectious Diseases and Immunology
 
Description Although enhanced macrophage-specific arginase activity is directly related to increased
parasite burden in cutaneous leishmaniasis (CL), the regulation and precise role of arginase
in the disease outcome of visceral leishmaniasis (VL) has yet to be explored. As in
CL, BALB/c mice infected with Leishmania donovani showed increased levels of arginase in
acute infection. Arginase 1 is the major isoform associated with infection and while the
IL-4-induced arginase pathway is operative in CL, IL-10 plays a crucial role in modulating
arginase activity in VL, although a synergism with IL-4 is required. IL-10, in combination
with IL-4, regulated both in vivo and ex vivo arginase 1 induction in a STAT6 and C/EBPbdependent
fashion. Further investigation toward the cause of such synergism suggests
that induction of a STAT3-dependent IL-10-mediated cascade in VL triggers the expression
and surface localization of the IL-4 receptor alpha (IL-4Ra) which, in turn, enhances IL-4
responsiveness toward STAT6 and C/EBPb-dependent signaling for arginase 1. This could
also offer a mechanistic explanation for the fact that, in spite of the low level of IL-4 in VL,
enhanced IL-4-Ra expression by IL-10 might markedly amplify IL-4-mediated arginase 1
signaling and provide a possible mechanism for synergistic induction of arginase 1.
 
Date 2011
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/99/1/EUROPEAN_JOURNAL_OF_IMMUNOLOGY%2C_41(4)%2C992%2D1003%2C2011_[72].pdf
Biswas, Arunima and Bhattacharya, Arijit and Kar, Susanta and Das, Pijush K (2011) Expression of IL-10-Triggered STAT3-Dependent IL-4Ra is Required for Induction of Arginase 1 in Visceral Leishmaniasis. European Journal Immunology., 41. pp. 992-1003.
 
Relation http://dx.doi.org/10.1002/eji.201040940
http://www.eprints.iicb.res.in/99/