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Cited by 27T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisImmunotherapy and Immune Responses

PU.1 Expression in T Follicular Helper Cells Limits CD40L-Dependent Germinal Center B Cell Development

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Awe, Olufolakemi, Hufford, Matthew M, Wu, Hao, Pham, Duy, Chang, Hua-Chen, Jabeen, Rukhsana, Dent, Alexander L, Kaplan, Mark H·2015·The Journal of Immunology
DOI 10.4049/jimmunol.1500780PMC PMC4592843
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Abstract

PU.1 is an ETS family transcription factor that is important for the development of multiple hematopoietic cell lineages. Previous work demonstrated a critical role for PU.1 in promoting Th9 development and in limiting Th2 cytokine production. Whether PU.1 has functions in other Th lineages is not clear. In this study, we examined the effects of ectopic expression of PU.1 in CD4(+) T cells and observed decreased expression of genes involved with the function of T follicular helper (Tfh) cells, including Il21 and Tnfsf5 (encoding CD40L). T cells from conditional mutant mice that lack expression of PU.1 in T cells (Sfpi1(lck-/-)) demonstrated increased production of CD40L and IL-21 in vitro. Following adjuvant-dependent or adjuvant-independent immunization, we observed that Sfpi1(lck-/-) mice had increased numbers of Tfh cells, increased germinal center B cells (GCB cells), and increased Ab production in vivo. This correlated with increased expression of IL-21 and CD40L in Tfh cells from Sfpi1(lck-/-) mice compared with control mice. Finally, although blockade of IL-21 did not affect GCB cells in Sfpi1(lck-/-) mice, anti-CD40L treatment of immunized Sfpi1(lck-/-) mice decreased GCB cell numbers and Ag-specific Ig concentrations. Together, these data indicate an inhibitory role for PU.1 in the function of Tfh cells, germinal centers, and Tfh-dependent humoral immunity.

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  • Conditional deletion of Spi1 in T-lineage cells after DN2 has only modest effects on T cells as a whole, limited to selective reduction of IL-9-producing T-cells and some loss of restraint on γδ T cells and Tfh activity.

    “if Spi1 is conditionally deleted in T-lineage cells only after the cells have passed the DN2 stage, there are very modest effects on T cells as a whole, apparently limited to selective reduction of IL-9-producing T-cells (74), and some loss of restraint on γδ T cells and T follicular helper cell activity (75, 76).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [76]

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Cited by

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Authors
Awe, O., Hufford, M. M., Wu, H., Pham, D., Chang, H.-C., Jabeen, R., Dent, A. L., & Kaplan, M. H.
Affiliations
  • Indiana University Indianapolis (US)
  • Indiana University School of Medicine (US)
  • Indiana University – Purdue University Indianapolis (US)
Corresponding author
  • Awe, Olufolakemi
  • Pham, Duy
  • Jabeen, Rukhsana
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2015-10
Volume
195
Issue
8
Pages
3705-3715
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.1500780
PMC
PMC4592843
OpenAlex
W1434467868
Cited by
27
References
7
Citations by year
2024: 4 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 5
FWCI
1.81
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • IUScholarWorks (Indiana University) (submittedVersion)
  • PMC
Funders
  • U.S. Public Health Service (F31 AL100542)
  • National Heart, Lung, and Blood Institute (T32HL007910)
  • National Institute of Allergy and Infectious Diseases (R03AI110987, F31AI100542, R21AI113523, R01AI057459, T32AI060519)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
PU.1, T follicular helper cells, germinal center B cells, CD40 ligand, IL-21, T cell differentiation, humoral immunity, conditional mutant mice, antibody production
MeSH terms
Interleukin-21, Proto-Oncogene Protein Spi-1, Animals, B-Lymphocytes, Gene Expression Regulation, T-Lymphocytes, Helper-Inducer, Interleukins, Proto-Oncogene Proteins, Trans-Activators, Mice, Knockout, Germinal Center, CD40 Ligand, Mice, Immunity, Humoral

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