A Study of the Changes of T Helper 17 Cells and Regulatory T Cells in Herpes Zoster

( Min Sung Kim ),( Dong Jin Kim ),( Chan Ho Na ),( Bong Seok Shin ) 대한피부과학회 2017 Annals of Dermatology Vol.29 No.5

Background: Immunosuppression and age-related deficiencies in cell-mediated immunity are important factors for the reactivation of latent varicella-zoster virus (VZV). CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells and T helper 17 (Th17) cells are closely associated with various viral infections. Objective: We analyzed Treg cells and Th17 cells in patients with herpes zoster and investigated their relationship with the reactivation of latent VZV. Methods: Treg and Th17 cells in peripheral blood and the ratio of Th17 to Treg cells were examined in patients with herpes zoster and healthy controls. Changes between pre-treatment and post-treatment estimates of Treg and Th17 cells and clinical parameters in patients with herpes zoster were also analyzed. Results: The proportion of circulating Th17 cells and the Th17/Treg cell ratio were significantly higher in patients with herpes zoster than controls (p=0.012, 0.013), but there was no significant difference in the proportion of Treg cells between groups. There was no significant difference in the proportions of Treg and Th17 cells and the Th17/Treg cell ratio before and after treatment and between the non-postherpetic neuralgia and postherpetic neuralgia groups. Changes in Treg and Th17 cells and the Th17/Treg cell ratio were not significantly correlated with changes in the visual analog scale. Body surface area was significantly correlated with Treg cells, Th17 cells, and the Th17/Treg cell ratio (p=0.022, 0.002, 0.004). Conclusion: An imbalance between Th17 and Treg cells is associated with the reactivation of VZV, which may contribute to pathogenesis of herpes zoster. (Ann Dermatol 29(5) 578∼585, 2017)

P158 A study of the changes of Th17 cells and regulatory T cells in herpes zoster

( Bae In-ho ),( Kim Dong-jin ),( Na Chan-ho ),( Kim Min-sung ),( Shin Bong-seok ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2

<div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div> Background: Although the mechanisms involved in reactivation of latent varicella-zoster virus (VZV) are unclear, the immunosuppression is an important factor involved in reactivation. CD4+CD25+Foxp3+ regulatory T cells (Treg) and T-hepler 17 cells (Th17) are closely associated with a various viral infections. Objectives: In this study, we aimed to investigate the changes of Treg cells and Th17 cells in herpes zoster patients. Methods: The percentage of circulating Th17 cells, Treg cells, and ratio of Th17 to Treg cells were examined in herpes zoster patients and controls. The changes of Treg and Th17 cells between pre-treatment and post-treatment and clinical parameters in herpes zoster patients were also analyzed. Results: There were significant difference in circulating Th17 cells proportion and ratio of Th17 to Treg cells in herpes zoster patients compare to control. However, there was no significant difference in Treg cells proportion in herpes zoster patients compared to control. There was no significant difference in Treg, Th17 cells and ratio of Th17 to Treg cells between pre-treatment and post-treatment. There was significant correlation between body surface area (BSA) and Treg cells, Th17 and the ratio of Th17 to Treg cells. Conclusion: These findings provide that there is an imbalance in Th17 and Treg cells associated with reactivation of VZV, which may contribute to pathogenesis of herpes zoster.

건선환자의 말초혈액 내 Th17세포와 Regulatory T세포의 균형에 관한 연구

나찬호 ( Chan Ho Na ),김동진 ( Dong Jin Kim ),김민성 ( Min Sung Kim ),신봉석 ( Bong Seok Shin ) 대한피부과학회 2016 大韓皮膚科學會誌 Vol.54 No.4

Background: Although the pathogenesis of psoriasis is not fully understood, recent studies suggest that an imbalance of T-helper 17 cells (Th17) and CD4+CD25+Foxp3+ regulatory T cells (Treg) is associated with psoriasis. However, the association between the imbalance of Th17 and Treg cells and psoriasis still remains controversial. Objective: In this study, the proportion of Th17 and Treg cells from peripheral blood were evaluated in patients with psoriasis and normal controls. Methods: The proportion of Th17 and Treg cells from peripheral blood were examined by flow cytometry in psoriasis patients (n=20) and age-matched healthy controls (n=23). The correlation between Th17 and Treg cells and the clinical parameters in psoriasis patients were also analyzed. Results: There were significant increases in the proportion of circulating Th17 cells and the ratio of Th17 to Treg cells in psoriasis patients compared to control (p=0.001 and p=0.002, respectively). In contrast to the Th17 cells, there was no significant difference in the proportion of Treg cells in psoriasis patients compared to control (p=0.310). The ratio of Th17 to Treg cells was positively correlated with body surface area (BSA) (p=0.038). In addition, although the ratio of Th17 to Treg cells increased along with psoriasis area severity index (PASI) score, there was no significant correlation (p=0.062). Conclusion: These findings show that there exists an imbalance in Th17 and Treg cells in psoriasis, which may contribute to its pathogenesis and involved surface area. (Korean J Dermatol 2016;54(4):268~274)

인간의 말초혈액에서 염증성 사이토카인에 의한 Th17 세포의 분화에 미치는 영향

허유정 ( Yu Jung Heo ),박미경 ( Mi Kyung Park ),주지현 ( Ji Hyeon Ju ),박경수 ( Kyung Su Park ),조미라 ( Mi La Cho ),김호연 ( Ho Youn Kim ) 대한류마티스학회 2009 대한류마티스학회지 Vol.16 No.2

Objective: IL-17-producing T cells (Th17 cells) have been identified as a distinct lineage of CD4+ T helper cells in mice. Since this discovery, many efforts have been made to investigate the characteristics and the role of human Th17 cells and the factors involved in their differentiation. This study was undertaken to assess the effects of cytokines and stimulatory conditions on the differentiation of human CD4+ T cells into Th17 cells. Methods: Peripheral blood CD4+ T cells were isolated from healthy humans and then these cells were cultured with using various stimulatory conditions. The Th17 cells and regulatory T (Treg) cells were detected by flow cytometry (FACs). The related gene expressions of cytokines, transcription factors and chemokine receptors were determined by ELISA and RT-PCR. Results: In the presence of inflammatory cytokines, TNFa and IL-1b, the human CD4+ T cells rapidly produced IL-17 in response to anti-CD3/anti-CD28 stimulation, whereas, with anti-CD3/ anti-CD28 stimulation alone, the CD4+ T cells expressed low levels of IL-17. TNFa and IL-1b were also important inducers of IL-22 production. IL-6 and IL-23 up-regulated the RORgammat, CCR4 and CCR6 expressions in the human CD4+ T cells. In response to TGF-b and IL-2, the human CD4+ T cells were rapidly induced to express FoxP3, IL-10 and CCR7, as compared with anti-CD3/anti-CD28 stimulation alone. Conclusion: The effect of inflammatory cytokines on the differentiation of human Th17 cells may help us to understand their pathogenic role. Moreover, the differential expression of chemokine receptors and transcription factors of the subsets of CD4+ T cells with the different features of Th17 and Treg, may raise new issues concerning the pathogenesis of autoimmune inflammatory diseases.

IL-33-matured dendritic cells promote Th17 cell responses via IL-1β and IL-6

Park, Su-Ho,Kim, Myun Soo,Lim, Hui Xuan,Cho, Daeho,Kim, Tae Sung Elsevier 2017 Cytokine Vol.99 No.-

<P><B>Abstract</B></P> <P>IL-33 is associated with a variety of autoimmune diseases, such as sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Although IL-33 is mainly involved in the induction of Th2 cells, however, the relationship between IL-33 and Th17 cells is still largely unknown. In this study, we investigated the effects of IL-33 on DC-mediated CD4<SUP>+</SUP> T cell activation and Th17 cell differentiation because DCs are essential cells for presenting self-antigens to CD4<SUP>+</SUP> T cells in autoimmune disease conditions. OT-II mice were injected with IL-33-treated DCs or untreated DCs that were primed by OVA<SUB>323-339</SUB> peptide, and their Th17 cell responses were compared. Th17 cell population and IL-17 expression levels were significantly increased in draining lymph nodes of mice injected with IL-33-treated DCs, compared with those in mice injected with untreated DCs. IL-33 treatment maturated DCs to present self-antigens and to increase production of proinflammatory cytokines such as IL-1β and IL-6, which have a crucial role in Th17 cell differentiation. We found that the IL-33-matured DCs enhanced the expression of an early T cell activation marker (CD69) and the Th17 master transcription factor (RORγt), but IL-33 did not directly affect CD4<SUP>+</SUP> T cell differentiation or increase Th17 polarization. Notably, neutralizing IL-1β and/or IL-6 significantly decreased IL-17 expression levels and Th17 cell population which were increased by the coculture of CD4<SUP>+</SUP> T cells with IL-33-matured DCs, indicating that IL-33 may induce Th17 cell responses via IL-1β and IL-6 derived from IL-33-matured DCs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> IL33 enhances Th17 cell differentiation through DC maturation. </LI> <LI> IL33 does not directly induce differentiation of naïve CD4<SUP>+</SUP> T cells to Th17 cells. </LI> <LI> IL33-matDCs increase surface molecule-expressions driving T cell activation. </LI> <LI> IL33-matDCs promote Th17 cell responses via DC-derived IL-1β and IL-6. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Bone Marrow-derived Mesenchymal Stem Cells Affect Immunologic Profiling of Interleukin-17-secreting Cells in a Chemical Burn Mouse Model

이자영,정현정,김미금,위원량 대한안과학회 2014 Korean Journal of Ophthalmology Vol.28 No.3

Purpose: This study investigated interleukin (IL)-17-secreting cell involvement in sterile inflammation, and evaluatedthe effect of mesenchymal stem cells (MSCs) on IL-17-secreting cell immunologic profiling. Methods: Twenty mice were sacrificed at time points of 6 hours, 1 day, 1 week, and 3 weeks (each group, n =5) after the cornea was chemically injured with 0.5N NaOH; IL-17 changes in the cornea were evaluated usingenzyme-linked immunosorbent assay. Further, IL-17 secreting cells were assessed in the cervical lymph nodesby a flow cytometer. Rat MSCs were applied intraperitoneally in a burn model (n = 10), IL-17-secreting T helper17 (Th17) cell and non-Th17 cell changes were checked using a flow cytometer in both cornea and cervicallymph nodes at 1week, and compared with those in the positive control (n = 10). Results: IL-17 was highest in the cornea at 1 week, while, in the cervical lymph nodes, IL-17-secreting cellsshowed early increase at 6 hours, and maintained the increase through 1 day to 1 week, and levels returnedto the basal level at 3 weeks. Specifically, the non-Th17 cells secreted IL-17 earlier than the Th17 cells. Whenthe MSCs were applied, IL-17 secretion was reduced in CD3(+)CD4(-)CD8(-), CD3(+)CD4(+)CD8(-), and CD3(+)CD4(-)CD8(+) cells of the cervical lymph nodes by 53.7%, 43.8%, and 50.8%, respectively. However, in thecornea, IL-17 secretion of CD3(+)CD4(-)CD8(-) cells was completely blocked. Conclusions: The results indicated that both IL-17-secreting non-Th17 and Th17 cells were involved in the chemicalburn model, and MSCs appeared to mainly modulate non-Th17 cells and also partially suppress the Th17 cells.

Intravenous Immunoglobulin Controls Th17 Cell-Mediated Osteoclastogenesis

김경운,김해림,김보미,원지연,이경언,이상헌 대한면역학회 2019 Immune Network Vol.19 No.4

The purpose of this study was to determine the regulatory role of intravenous Ig (IVIg) in Th17 cytokine–induced RANK ligand (RANKL) expression and osteoclast (OC) differentiation from OC precursors (pre-OC). Human CD14+ monocytes were isolated and stimulated by Th17 cytokines (IL-17, IL-21, and IL-22) and RANKL expression was investigated using a real-time PCR. CD14+ monocytes were incubated with RANKL, Th17 cytokines, and M-CSF, with/without IVIg, and OC differentiation was determined by counting tartrate-resistant acid phosphatase-positive multinucleated cells. OC differentiation was investigated after monocytes were cocultured with Th17 cells in the presence of IVIg. Th17 cell differentiation was determined using enzyme-linked immunosorbent assay and flow cytometry after CD4+ T cells were cultured with IVIg under Th17 condition. Th17 cytokines stimulated monocytes to express RANKL and IVIg suppressed the Th17 cytokine-induced RANKL expression. OCs were differentiated when pre-OC were cocultured with RANKL or Th17 cytokines and IVIg reduced the osteoclastogenesis. IVIg also decreased osteoclastogenesis when pre-OC were cocultured with Th17 cells. IVIg decreased both Th17 and Th1 cell differentiation while it did not affect Treg cell differentiation. In summary, IVIg inhibited Th17 cytokine-induced RANKL expression and OC differentiation. IVIg reduced osteoclastogenesis when monocytes were cocultured with Th17 cells. IVIg also reduced Th17 polarization. IVIg could be a new therapeutic option for Th17 cell–mediated osteoclastogenesis.

Th17 Cells Are Not Directly Associated with Renal Ischemia-Reperfusion Injury

( Yoon Kyung Chang ),( Dae Eun Choi ),( Jin Young Jeong ),( Hye Jin Choi ),( Beom Jin Lim ) 대한신장학회 2011 Kidney Research and Clinical Practice Vol.30 No.3

Purpose: Interleukin-17-producing T cell (Th17 cell) is a newly discovered subtype of helper T cell. Its function and importance in the pathogenesis of a broad range of immune diseases are under active investigation. However, little is currently known about the role of Th17 cells in ischemia-reperfusion (IR) injury of the kidney, a common pathophysiologic occurrence in various renal disease processes. Methods: We measured the number of infiltrated T lymphocytes and Th17 cells in C57Bl/6 mouse kidneys in sham-operated controls and following varying degrees of renal IR injury induced by renal pedicle clamping and reperfusion. The cell count results were compared to accompanying histologic damage and serum creatinine levels after 35 min and 45 min of ischemia, and following reperfusion of 48, 72, 96, and 168 hrs. Results: The number of T lymphocytes increased as ischemia time increased. However, the number of Th17 cells was not significantly affected by prolonged ischemia and reperfusion. Furthermore, the degree of histologic damage and serum creatinine levels did not correlate with the T lymphocyte and Th17 cell count numbers. Conclusion: We did not observe any evidence that Th17 cells are directly linked to renal tissue damage caused by IR injury. The role and importance of helper T cells in renal IR injury need to be evaluated further in the light of the interaction with Th1, Th2, and regulatory T cells rather than Th17 alone.

IL-17A and Th17 Cells Contribute to Endometrial Cell Survival by Inhibiting Apoptosis and NK Cell Mediated Cytotoxicity of Endometrial Cells via ERK1/2 Pathway

Kang Young-Ju,Cho Hee Jun,Lee Yunhee,Park Arum,Kim Mi Jeong,Jeung In Cheul,Jung Yong-Wook,Jung Haiyoung,Choi Inpyo,Lee Hee Gu,Yoon Suk Ran 대한면역학회 2023 Immune Network Vol.23 No.2

Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.

Th17 Cell and Inflammatory Infiltrate Interactions in Cutaneous Leishmaniasis: Unraveling Immunopathogenic Mechanisms

Abraham U. Morales-Primo,Ingeborg Becker,Claudia Patricia Pedraza-Zamora,Jaime Zamora-Chimal The Korean Association of Immunobiologists 2024 Immune Network Vol.24 No.2

The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4⁺ T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8⁺ T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8⁺ T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4⁺ T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1β, TGF-β, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.