22 research outputs found
The 1918 Influenza Pandemic and Japanese Government-General of Koreaโs Preventive Measures against Epidemics
์ํ ํผํผ๋ถ์ผ์ ํผ๋ถ๊ฑฐ์ฃผ T ์ธํฌ์์ CCCTC-๊ฒฐํฉ ์ธ์์ ์ญํ
์๊ณผํAtopic dermatitis (AD) is a highly pruritic, chronic relapsing inflammatory skin disease characterized by significant T-cell infiltration and frequently recurs in the same areas of the skin, and even resolved skin keeps the diseaseโs memory. While the role of tissue-resident memory T cells (TRM cells) has been well studied in the chronic inflammatory skin diseases such as psoriasis which relapses in the same sites, that of TRM cells in AD has not been investigated in detail. CCCTC-binding factor (CTCF) is a ubiquitously expressed regulator of fundamental genetic processes including transcription, intra- and interchromosomal interactions, and chromatin structure. Because of its critical role in genome function, CTCF binding patterns have long been assumed to be largely invariant across different cellular environments. Therefore, the functional analysis of CTCF in the different types of cells and tissues would further expand our knowledge in the roles of CTCF. In this dissertation, I focus on the role of CTCF in TRM cells in AD. To explore the function of TRM cells in AD. I examined how many TRM cells expressing the canonical maker CD69 and CD103 existed and which cytokines including IL-4, IL13, IL-17, IL-22 and IFN-ฦด these cells produced in human AD and age-matched normal skin tissues and in AD-like mouse models generated with the treatment of allergens (1-Fluoro-2,4-dinitrobenzene (DNFB), oxazolone, ovalbumin) or mixture thereof. I also evaluated which AD triggering factors affected the development of TRM cells and the production of cytokines using purified cutaneous lymphocyte-associated antigen (CLA) expressing T cells from normal peripheral blood mononuclear cells (PBMCs). Finally, using transcriptomics, I evaluated the cytokine signatures and novel genes associated with skin TRM cells compared to migratory memory T cells (TMM) in human normal and AD skin. I observed that CD69+ and CD103+ TRM cells significantly infiltrated into chronic AD skin compared to normal skin. However, normal skin mostly ontained CD103- and CD69- T cells. Significant numbers of CD69+ AD TRM cells produced Th2 cytokines (IL-4, IL-13), Th17 cytokines (IL-17, IL-22), and Th1 cytokines (IFN-ฦด). In AD-like mouse model induced by allergen mixture, CD69+ skin TRM cells produced various cytokines (IL-4, IL-17, IL-22 and IFN-ฦด) compared to a single allergen induced AD-like mouse models. During the incubation of CLA+ T cells for 3 weeks, CD69+ expression of CD4+ and CD8+ T cells was continuously increased in a time-dependent manner while CD103+ expression was not significantly changed. Repeated exposure to thymic stromal lymphopoietin (TSLP), a well-known AD triggering factor, induced more CD69+ TRM cells during the development of AD TRM. Various cytokines (IL4, IL17, IL-22 and IFN-ฦด) were considerably produced in CD69+ TRM cells compared to CD69- T cells in AD mimicking mice after 3 weeks. I further confirmed that AD CD69+ TRM cells expressed higher levels of Th1, Th2, Th17 and Th22 cytokines and their transcription factors (T-bet, GATA3, RORฦดt and Ahr) showing unique transcriptional profiles distinct from those of AD CD69- TMM cells or normal skin CD69+ TRM cells. I further identified various genes associated with tissue egress and residency specific to AD TRM cells. Among those, I chose CCCTC-binding factor (CTCF) because of its role in immune diseases. I confirmed the decrease of CTCF in CD69+ TRM cells from AD patient skin. In conclusion, CTCF may play an important role in regulating the expression of multiple cytokines from CD69+ TRM cells in AD skin. Through this mechanism, repeated exposure to AD-triggering factors might induce AD TRM cells to produce multiple cytokines and sustain the recurrence and chronicity of AD patients.
์ํ ํผํผ๋ถ์ผ์ ์์์ฆ์ ๋๋ฐํ ๋ง์ฑ ์ฌ๋ฐ์ฑ์ ์ผ์ฆ์ฑ ์งํ์ผ๋ก, ์ธ๋ถํ๊ฒฝ์ผ๋ก๋ถํฐ ์นจ์
ํ ํญ์ ๋ฌผ์ง๊ณผ ์งํผ์ ๋ฉด์ญ์ธํฌ์ ์ํด ์ผ๊ธฐ๋๋ ๋ฉด์ญ๋ฐ์๊ณผ ํผ๋ถ์ ๊ฐ์ ์๋ฆฌ์ ๊ณ์ํด์ ๋ค์ ๋ฐ์ํ๋ ๊ฒ์ ํน์ง์ผ๋ก ํ๋ค. ํผ๋ถ ๊ฑฐ์ฃผ T ์ธํฌ (TRM ์ธํฌ)๋ ๊ธฐ์ต T ์ธํฌ์ ํ ์ข
๋ฅ๋ก ๋ง์ด ์กฐ์ง์ ์ค๋ ๊ธฐ๊ฐ ๋์ ๊ณ์ํด์ ์กด์ฌํ๋ ์ธํฌ๋ก ์๋ ค์ ธ ์์ผ๋ฉฐ, ์์ฅ๊ด, ๊ธฐ๋, ํผ๋ถ์ ๊ฐ์ ์์ฃผ์ ํ๊ฒฝ ์ฌ์ด์ ์ ์ ์ ์ํผ ๋ง ์กฐ์ง์ ์กด์ฌํ๋ค. CCCTC-binding factor (CTCF)๋ DNA ๊ฒฐํฉ zinc-finger ๋จ๋ฐฑ์ง๋ก์, ๊ณ ์ฐจ์ ํฌ๋ก๋งํด ๊ตฌ์กฐ ๊ฒฐ์ ์ ์ค์ํ๊ฒ ๊ด์ฌํ์ฌ ๋ค์ํ ๋ถ์์๋ฌผํ์ ๊ธฐ์ ์ ํตํด ์ ์ ์ ๋ฐํ์ ์กฐ์ ํ๋ค๊ณ ์๋ ค์ ธ ์๋ ์ ์ ์์ด๋ค. ๋ณธ์ธ์ ์ํ ํผํผ๋ถ์ผ์์์ ํผ๋ถ ๊ฑฐ์ฃผ T ์ธํฌ์ ์ญํ ๊ณผ ์ฑ์์ ํ์ธํ๊ณ ์ ํ์๊ณ , ํผ๋ถ ๊ฑฐ์ฃผ T ์ธํฌ๊ฐ ์ํ ํผํผ๋ถ์ผ์ ์
ํ์ํค๋๋ฐ ์์ด์ CTCF ๋จ๋ฐฑ์ง์ ๋ฐํ ๋ฐ ๊ธฐ๋ฅ์ ์ฐ๊ตฌํ์๋ค. CD69+ ๋ฐ CD103+ TRM ์ธํฌ๊ฐ ์ ์ ํผ๋ถ์กฐ์ง์ ๋นํด ์ํ ํผํผ๋ถ์ผ ํ์์ ํผ๋ถ์กฐ์ง์ ํ์ ํ ์นจํฌํ๋ ๊ฒ์ ๊ด์ฐฐํ์๊ณ , ์ ์ ํผ๋ถ์กฐ์ง์๋ ๋น๊ต์ CD103- ๋ฐ CD69- ์ธํฌ๊ฐ ๋ง์ด ๋ฐํ๋๋ ๊ฒ์ ํ์ธํ์๋ค. ๋ํ, ๋ฉด์ญํ๊ด์ผ์๋ฒ์ ํตํด CD69+ AD TRM ์ธํฌ๊ฐ Th2 ์ฌ์ดํ ์นด์ธ (IL-4, IL-13), Th17 ์ฌ์ดํ ์นด์ธ (IL-17, IL-22) ๋ฐ Th1 ์ฌ์ดํ ์นด์ธ (IFN-ฦด)๊ณผ ๊ฐ์ ๋ค์ํ ์ฌ์ดํ ์นด์ธ๋ค์ ๋ถ๋นํ๋ ๊ฒ์ ํ์ธํ์๋ค. ์ํ ํผํผ๋ถ์ผ๊ณผ ์ ์ฌํ ๋ง์ฐ์ค ๋ชจ๋ธ (DNFB, ์ฅ์ฌ์กธ๋ก , ์ค๋ฐ๋ถ๋ฏผ) ํผ๋ถ์กฐ์ง์ CD69+ TRM ์ธํฌ์ ๋นํด ๋ค์ํ ์๋ฌ์ ์ ๋
ธ์ถ๋๋ ์ํ ํผํผ๋ถ์ผ ํ์์ ์ ์ฌํ๊ฒ ์ด ์๋ฌ์ ๋ค์ ๋ชจ๋ ํผํฉํ์ฌ ์ ๋ฐํ ๋ง์ฐ์ค ๋ชจ๋ธ ํผ๋ถ์กฐ์ง์ CD69+ TRM ์ธํฌ์์ ์ญ์ ๋ค์ํ ์ฌ์ดํ ์นด์ธ๋ค์ ๋ง์ด ๋ถ๋นํ๋ ๊ฒ์ ํ์ธํ์๋ค. 3์ฃผ๊ฐ์ CLA+ T ์ธํฌ ๋ฐฐ์ ๋์, CD4+ ๋ฐ CD8+ T ์ธํฌ์ CD69+ TRM ์ธํฌ์ ๋ฐํ์ ์๊ฐ์ด ์ง๋ ์๋ก ์ง์์ ์ผ๋ก ์ฆ๊ฐ ํ์๊ณ , ์ํ ํผํผ๋ถ์ผ๊ณผ ์ ์ฌํ ํ๊ฒฝ์ ์กฐ์ฑํด ์ฃผ์์ ๋, ๋ ๋ง์ CD69+ TRM ์ธํฌ ๋ฐ ๋ค์ํ ์ฌ์ดํ ์นด์ธ๋ค์ด ์์ฑ๋๋ ๊ฒ์ ํ์ธํ์๋ค. ์ด๋ฅผ ์ฆ๋ช
ํ๊ธฐ ์ํด AD CD69- TMM ๋ฐ CD69+ TRM ์ธํฌ์์ RNA๋ฅผ ์ป์ด microarray ๋ถ์์ ์งํํ์๋ค. ๊ทธ ๊ฒฐ๊ณผ CD69+ TRM ์ธํฌ์์ Th1, Th2, Th17 ๋ฐ Th22 ์ฌ์ดํ ์นด์ธ๊ณผ ๊ทธ ์ ์ฌ์ธ์ (T-bet, GATA3, RORฦดt ๋ฐ Ahr)๋ค์ด ๋์ ์์ค์ ๋ํ๋ด๋ ๊ฒ์ ํ์ธํ์๋ค. ์ ์ฒด 47322 ๊ฐ์ ์ ์ ์ ์ค AD CD69- TMM ์ธํฌ์ ๋น๊ตํ์์ ๋ AD CD69+ TRM ์ธํฌ์์ CTCF ์ ์ ์๊ฐ ๋๋ ทํ๊ฒ ๊ฐ์๋์๋ค. ์ด๋ฅผ ๊ฒ์ฆํ๊ธฐ ์ํด, ๋ณธ์ธ์ CTCF ๋จ๋ฐฑ์ง์ ๋ฐํ์ด ์ ์์ธ์ ํผ๋ถ์กฐ์ง์ ๋นํด ์ํ ํผํผ๋ถ์ผ ํ์์ ํผ๋ถ์กฐ์ง์์, ๋ํ CD69- TMM ์ธํฌ์ ๋นํด CD69+ TRM ์ธํฌ์์ ํ์ ํ๊ฒ ๊ฐ์๋จ์ ๋ฉด์ญํํ์ผ์๋ฒ๊ณผ ๋ฉด์ญํ๊ด์ผ์, real-time PCR ๋ฐ shRNA๋ฅผ ํตํด ํ์ธํ์๋ค. ๊ฒฐ๋ก ์ ์ผ๋ก, ๋ณธ ์ฐ๊ตฌ๋ฅผ ํตํด ์ํ ํผํผ๋ถ์ผ ์ ๋ฐ ์์ธ์ ๋ฐ๋ณต์ ์ผ๋ก ๋
ธ์ถ๋๋ฉด CTCF ์ ์ ์ ๋ฐํ์ ๊ฐ์๋์ด ์ํ ํผํผ๋ถ์ผ์ CD69+ TRM ์ธํฌ๋ฅผ ์กฐ์ ํ๊ฒ ๋จ์ ํ์ธํ์๊ณ , ์ด๋ก ์ธํด CD69+ TRM ์ธํฌ๊ฐ ๋ค์ํ ์ฌ์ดํ ์นด์ธ๋ค์ ์์ฑํ๊ฒ ๋์ด์ ๊ฒฐ๋ก ์ ์ผ๋ก ์ํ ํผํผ๋ถ์ผ์ ์
ํ๋ฅผ ์ ๋ํ๊ฒ ๋จ์ ํ์ธํ์๋ค.open๋ฐ
A study on the correlation between passive voice and the function of showing respect in ancient chinese - Focusing on A่งV sentence
Positive reactions to nickel on a patch test do not predict clinical outcome of nickel alloy-based atrial septal defect occluder implantation
BACKGROUND: Patch testing is thought to be necessary prior to metal device implantation to rule out metal allergy-related complications; however, there are controversies over the effects of nickel allergy on the outcome of nickel alloy-based device implantation.
OBJECTIVE: This study aimed to evaluate the adverse events in a Korean population of nickel allergy patients who underwent atrial septal defect (ASD) closure with a nickel-titanium alloy-based device.
METHODS: We retrospectively reviewed the medical records of patients who underwent ASD closure with a nitinol device.
RESULTS: Among 38 patients who had ASD closure, 4 of 5 nickel-allergic patients and 10 of the 33 non-nickel-allergic patients had post-closure complications. All patients fared well, without device failure culminating in device removal.
CONCLUSION: In this study, positive reactions to nickel in a patch test were not associated with adverse early or late outcomes following ASD closure with a nickel alloy-based device.ope