Increased Development of Th1, Th17, and Th1.17 Cells Under T1 Polarizing Conditions in Juvenile Idiopathic Arthritis
In juvenile idiopathic arthritis (JIA) inflammatory T cells and their produced cytokines are drug targets and play a role in disease pathogenesis. Despite their clinical importance, the sources and types of inflammatory T cells involved remain unclear. T cells respond to polarizing factors to initia...
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| Published in: | Frontiers in immunology Vol. 13; p. 848168 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Switzerland
Frontiers Media S.A
04-07-2022
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | In juvenile idiopathic arthritis (JIA) inflammatory T cells and their produced cytokines are drug targets and play a role in disease pathogenesis. Despite their clinical importance, the sources and types of inflammatory T cells involved remain unclear. T cells respond to polarizing factors to initiate types of immunity to fight infections, which include immunity types 1 (T1), 2 (T2), and 3 (T17). Polarizing factors drive CD4
T cells towards T helper (Th) cell subtypes and CD8
T cells towards cytotoxic T cell (Tc) subtypes. T1 and T17 polarization are associated with autoimmunity and production of the cytokines IFNγ and IL-17 respectively. We show that JIA and child healthy control (HC) peripheral blood mononuclear cells are remarkably similar, with the same frequencies of CD4
and CD8
naïve and memory T cell subsets, T cell proliferation, and CD4
and CD8
T cell subsets upon T1, T2, and T17 polarization. Yet, under T1 polarizing conditions JIA cells produced increased IFNγ and inappropriately produced IL-17. Under T17 polarizing conditions JIA T cells produced increased IL-17. Gene expression of IFNγ, IL-17, Tbet, and RORγT by quantitative PCR and RNA sequencing revealed activation of immune responses and inappropriate activation of IL-17 signaling pathways in JIA polarized T1 cells. The polarized JIA T1 cells were comprised of Th and Tc cells, with Th cells producing IFNγ (Th1), IL-17 (Th17), and both IFNγ-IL-17 (Th1.17) and Tc cells producing IFNγ (Tc1). The JIA polarized CD4
T1 cells expressed both Tbet and RORγT, with higher expression of the transcription factors associated with higher frequency of IL-17 producing cells. T1 polarized naïve CD4
cells from JIA also produced more IFNγ and more IL-17 than HC. We show that in JIA T1 polarization inappropriately generates Th1, Th17, and Th1.17 cells. Our data provides a tool for studying the development of heterogeneous inflammatory T cells in JIA under T1 polarizing conditions and for identifying pathogenic immune cells that are important as drug targets and diagnostic markers. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present address: Tashawna Esmond, Department of Molecular and Cellular Physiology, Louisiana State University Health Science Center, Shreveport, LA, United States These authors have contributed equally to this work and share senior authorship This article was submitted to Autoimmune and Autoinflammatory Disorders, a section of the journal Frontiers in Immunology Reviewed by: Bas Vastert, University Medical Center Utrecht, Netherlands; Mirjam Kool, Nutricia Research (Netherlands), Netherlands Edited by: Lindsay B. Nicholson, University of Bristol, United Kingdom |
| ISSN: | 1664-3224 1664-3224 |
| DOI: | 10.3389/fimmu.2022.848168 |