Identification of Novel Molecular Markers of Human Th17 Cells

Sałkowska, Anna; Karaś, Kaja; Karwaciak, Iwona; Walczak‐Drzewiecka, Aurelia; Krawczyk, Mariusz; Sobalska‐Kwapis, Marta; Dastych, Jarosław; Ratajewski, Marcin

doi:10.3390/cells9071611

Cited by 32 publications

(23 citation statements)

References 96 publications

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“…Next, 5 μg RNA was used to obtain cDNA using the Maxima First Strand cDNA Synthesis Kit for RT-quantitative PCR (Thermo Fisher Scientific, Waltham, MA, USA). Real-time RT-PCR was performed using SYBR Green I Master Mix on a LightCycler 480 (Roche, Basel, Switzerland) in a 384-well white plate under the following conditions: 95 °C for 5 min followed by 45 cycles of 95°C for 10 s, 60°C for 10 s, and 72°C for 20 s. Primers for TBX21 , RORγT , IL17A , and IL17F were described previously [ 19 , 20 , 21 ]. Primers for IFNG and TNF were designed using Primer3 [ 22 ] and QuantPrime [ 23 ], respectively.…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Proteins Induce IFNG in Th1 Lymphocytes Generated from CD4+ Cells from Healthy, Unexposed Polish Donors

et al. 2020

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The outbreak of the SARS-CoV-2 virus in December 2019 has caused the deaths of several hundred thousand people worldwide. Currently, the pathogenesis of COVID-19 is poorly understood. During the course of COVID-19 infection, many patients experience deterioration, which might be associated with systemic inflammation and cytokine storm syndrome; however, other patients have mild symptoms or are asymptomatic. There are some suggestions that impaired cellular immunity through a reduction in Th1 response and IFNG (interferon gamma) expression, as well as cross-reactivity with common cold coronaviruses, might be involved in the differential COVID-19 course. Here, we show that CD4+ cells isolated from unexposed healthy donors that were differentiated towards the Th1 lineage in the presence of SARS-CoV-2 proteins exhibited induction of IFNG. Interestingly, the same cells induced to differentiate towards a Th17 lineage did not exhibit changes in IFNG expression or Th17-related cytokines. This suggests the cellular response to SARS-CoV-2 viral proteins is primarily associated with Th1 lymphocytes and may be dependent on past infections with common cold coronaviruses or vaccinations that induce unspecific cellular responses, e.g., BCG (Bacillus Calmette-Guérin). Thus, our results might explain the high variability in the course of COVID-19 among populations of different countries.

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Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Proteins Induce IFNG in Th1 Lymphocytes Generated from CD4+ Cells from Healthy, Unexposed Polish Donors

et al. 2020

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“…S4b), which could suggest their interlinked participation in keeping inflammatory responses in check. Further, co-depletion of FOSL1 and FOSL2 induced a significant increase in levels of JUNB, CD70 and APOD, all of which have reported links to Th17regulation 2,6,15,45,46,72 (Fig. S3e and Fig.…”

Section: Perturbing Fos-like Proteins Triggers Important Changes In Th17 Gene-expression Programsmentioning

confidence: 87%

The AP-1 factorsFOSL1andFOSL2co-regulate human Th17 responses

Shetty

Tripathi

Junttila

et al. 2021

Preprint

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Th17 cells protect mucosal barriers, but their aberrant activity can cause autoimmunity. Molecular networks dictating human Th17 function are largely unexplored, and this hinders disease-studies. Here, we investigated the functions of the AP-1 proteins FOSL1 and FOSL2 in inducing human Th17 responses. Transient knockdown and over-expression strategies demonstrated the two proteins to inhibit Th17-cell identity, while revealing a novel cooperativity between their functions. Strikingly, FOSL1 plays different roles in human and mouse and FOSL-mediated Th17 regulation is opposed by the AP-1 factor, BATF. Genome- wide occupancy analysis indicated the co-localization of FOSL1, FOSL2 and BATF in the proximity of key Th17 genes. The functional interplay among these transcription factors (TFs) is potentially governed by sharing interactions with a common set of lineage-associated proteins. We further discovered that the genomic binding sites of these factors harbor a large number of disease-linked SNPs, many of which alter the ability of a given factor to bind DNA. Our findings thus provide crucial insights into the pathology of Th17-mediated diseases.

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“…Thus, APOD may participate in other SOX9-independent signaling pathways in the synovium tissue during OA progression. A recent study identified APOD as one of the novel molecular markers of human Th17 cells [ 59 ]. Although Th17 cells were initially investigated in RA due to their potency against autoimmune diseases [ 59 ], accumulating evidence suggests they are also increased in the OA [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

“…A recent study identified APOD as one of the novel molecular markers of human Th17 cells [ 59 ]. Although Th17 cells were initially investigated in RA due to their potency against autoimmune diseases [ 59 ], accumulating evidence suggests they are also increased in the OA [ 60 ]. Additionally, the high APOD protein level in the round ligament fat depot of severely obese women is associated with an improved inflammatory profile [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

Zheng

2020

IJMS

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Arthritis is the leading cause of disability among adults, while osteoarthritis (OA) is the most common form of arthritis that results in cartilage loss. However, accumulating evidence suggests that the protective hyaline cartilage should not be the sole focus of OA treatment. Particularly, synovium also plays essential roles in OA’s initiation and progression and warrants serious consideration when battling against OA. Thus, biomarkers with similar OA-responsive expressions in cartilage and synovium should be the potential targets for OA treatment. On the other hand, molecules with a distinguished response during OA in cartilage and synovium should be ruled out as OA therapeutic(s) to avoid controversial effects in different tissues. Here, to pave the path for developing a new generation of OA therapeutics, two published transcriptome datasets of knee articular cartilage and synovium were analyzed in-depth. Genes with statistically significantly different expression in OA and healthy cartilage were compared with those in the synovium. Thirty-five genes with similar OA-responsive expression in both tissues were identified while recognizing three genes with opposite OA-responsive alteration trends in cartilage and synovium. These genes were clustered based on the currently available knowledge, and the potential impacts of these clusters in OA were explored.

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Identification of Novel Molecular Markers of Human Th17 Cells

Cited by 32 publications

References 96 publications

SARS-CoV-2 Proteins Induce IFNG in Th1 Lymphocytes Generated from CD4+ Cells from Healthy, Unexposed Polish Donors

SARS-CoV-2 Proteins Induce IFNG in Th1 Lymphocytes Generated from CD4+ Cells from Healthy, Unexposed Polish Donors

The AP-1 factorsFOSL1andFOSL2co-regulate human Th17 responses

Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue

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