TY - JOUR
T1 - BHLHE40 promotes TH2 cell-mediated antihelminth immunity and reveals cooperative CSF2RB family cytokines
AU - Jarjour, Nicholas N.
AU - Bradstreet, Tara R.
AU - Schwarzkopf, Elizabeth A.
AU - Cook, Melissa E.
AU - Lai, Chin Wen
AU - Ching-Cheng Huang, Stanley
AU - Taneja, Reshma
AU - Stappenbeck, Thaddeus S.
AU - Van Dyken, Steven J.
AU - Urban,, Joseph F.
AU - Edelson, Brian T.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants R01AI113118 and R01AI132653 (to B.T.E.), T32AI007163 (to N.N.J.), and P30DK097948 (to S.C.-C.H.), a Burroughs Wellcome Fund Career Award for Medical Scientists (to B.T.E.), National Science Foundation Grant DGE-1745038 (to M.E.C.), and American Cancer Society Grant IRG-16-186-21 (to S.C.-C.H.). Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences Grant UL1TR002345 from the National Center for Advancing Translational Sciences of the National Institutes of Health.
Publisher Copyright:
© 2020 by The American Association of Immunologists, Inc.
PY - 2020/2/15
Y1 - 2020/2/15
N2 - The transcription factor BHLHE40 is an emerging regulator of the immune system. Recent studies suggest that BHLHE40 regulates type 2 immunity, but this has not been demonstrated in vivo.We found that BHLHE40 is required in T cells for a protective TH2 cell response in mice infected with the helminth Heligmosomoides polygyrus bakeri. H. polygyrus elicited changes in gene and cytokine expression by lamina propria CD4+ T cells, many of which were BHLHE40 dependent, including production of the common b (CSF2RB) chain family cytokines GM-CSF and IL-5. In contrast to deficiency in GM-CSF or IL-5 alone, loss of both GM-CSF and IL-5 signaling impaired protection against H. polygyrus. Overall, we show that BHLHE40 regulates the TH2 cell transcriptional program during helminth infection to support normal expression of Csf2, Il5, and other genes required for protection and reveal unexpected redundancy of common b chain-dependent cytokines previously thought to possess substantially divergent functions.
AB - The transcription factor BHLHE40 is an emerging regulator of the immune system. Recent studies suggest that BHLHE40 regulates type 2 immunity, but this has not been demonstrated in vivo.We found that BHLHE40 is required in T cells for a protective TH2 cell response in mice infected with the helminth Heligmosomoides polygyrus bakeri. H. polygyrus elicited changes in gene and cytokine expression by lamina propria CD4+ T cells, many of which were BHLHE40 dependent, including production of the common b (CSF2RB) chain family cytokines GM-CSF and IL-5. In contrast to deficiency in GM-CSF or IL-5 alone, loss of both GM-CSF and IL-5 signaling impaired protection against H. polygyrus. Overall, we show that BHLHE40 regulates the TH2 cell transcriptional program during helminth infection to support normal expression of Csf2, Il5, and other genes required for protection and reveal unexpected redundancy of common b chain-dependent cytokines previously thought to possess substantially divergent functions.
UR - http://www.scopus.com/inward/record.url?scp=85079020866&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1900978
DO - 10.4049/jimmunol.1900978
M3 - Article
C2 - 31900338
AN - SCOPUS:85079020866
SN - 0022-1767
VL - 204
SP - 923
EP - 932
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -