Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis
Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD). We aimed to investigate the role of NKT cells in AD development, especially in skin. Global proteomic and transcriptomic anal...
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| Veröffentlicht in: | Journal of allergy and clinical immunology 2021-05, Vol.147 (5), p.1764-1777 |
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| creator | Sun, ZhengWang Kim, Ji Hye Kim, Seo Hyeong Kim, Hye Ran Zhang, KeLun Pan, Youdong Ko, Min Kyung Kim, Bo Mi Chu, Howard Lee, Hee Ra Kim, Hye Li Kim, Ji Hyung Fu, Xiujun Hyun, Young-Min Yun, Ki Na Kim, Jin Young Lee, Dong Won Song, Seung Yong Lin, Charles P. Clark, Rachael A. Lee, Kwang Hoon Kupper, Thomas S. Park, Chang Ook |
| description | Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD).
We aimed to investigate the role of NKT cells in AD development, especially in skin.
Global proteomic and transcriptomic analyses were performed by using skin and blood from human healthy–controls and patients with AD. Levels of CXCR4 and CXCL12 expression in skin NKT cells were analyzed in human AD and mouse AD models. By using parabiosis and intravital imaging, the role of skin CXCR4+ NKT cells was further evaluated in models of mice with AD by using CXCR4–conditionally deficient or CXCL12 transgenic mice.
CXCR4 and its cognate ligand CXCL12 were significantly upregulated in the skin of humans with AD by global transcriptomic and proteomic analyses. CXCR4+ NKT cells were enriched in AD skin, and their levels were consistently elevated in our models of mice with AD. Allergen-induced NKT cells participate in cutaneous allergic inflammation. Similar to tissue-resident memory T cells, the predominant skin NKT cells were CXCR4+ and CD69+. Skin-resident NKT cells uniquely expressed CXCR4, unlike NKT cells in the liver, spleen, and lymph nodes. Skin fibroblasts were the main source of CXCL12. CXCR4+ NKT cells preferentially trafficked to CXCL12-rich areas, forming an enriched CXCR4+ tissue-resident NKT cells/CXCL12+ cell cluster that developed in acute and chronic allergic inflammation in our models of mice with AD.
CXCR4+ tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.
[Display omitted] |
| doi_str_mv | 10.1016/j.jaci.2020.11.049 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9272812</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S009167492100097X</els_id><sourcerecordid>2484158863</sourcerecordid><originalsourceid>FETCH-LOGICAL-c483t-f38ddd9aed56ddc5bb2983d5414c798b57b4b5b5d7efa4d9f1afc3b9c628d9e23</originalsourceid><addsrcrecordid>eNp9kU9rFTEUxYMo9rX6BVzIgBs388zfmQREKEVroeCi7TpkkjttpjOZMckU_PbN8GpRF65CTn73kHMPQu8I3hNMmk_DfjDW7ymmRSB7zNULtCNYtXUjqXiJdhgrUjctV0foOKUBlzuT6jU6YkyQRrZ4h-6u7n2oIyTvIOQqmLxGM1b3fhwhVteVhXFM1WJi9tYvJkPlQ2XXbALMa6rMht16W9R-NNNksp_Dhpg8L0V2EDct-_QGverNmODt03mCbr59vT77Xl_-OL84O72sLZcs1z2TzjllwInGOSu6jirJnOCE21bJTrQd70QnXAu94U71xPSWdco2VDoFlJ2gLwffZe0mcLakKoH0Ev1k4i89G6__fgn-Tt_OD1rRlkqyGXx8MojzzxVS1pNP2xoOkTXlkhMhZcMK-uEfdJjXGEo8TQWlWDAhSaHogbJxTilC__wZgvVWpB70VqTeitSE6FJkGXr_Z4znkd_NFeDzAYCyzAcPUSfrIVhwPoLN2s3-f_6PADWypw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2522053581</pqid></control><display><type>article</type><title>Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Sun, ZhengWang ; Kim, Ji Hye ; Kim, Seo Hyeong ; Kim, Hye Ran ; Zhang, KeLun ; Pan, Youdong ; Ko, Min Kyung ; Kim, Bo Mi ; Chu, Howard ; Lee, Hee Ra ; Kim, Hye Li ; Kim, Ji Hyung ; Fu, Xiujun ; Hyun, Young-Min ; Yun, Ki Na ; Kim, Jin Young ; Lee, Dong Won ; Song, Seung Yong ; Lin, Charles P. ; Clark, Rachael A. ; Lee, Kwang Hoon ; Kupper, Thomas S. ; Park, Chang Ook</creator><creatorcontrib>Sun, ZhengWang ; Kim, Ji Hye ; Kim, Seo Hyeong ; Kim, Hye Ran ; Zhang, KeLun ; Pan, Youdong ; Ko, Min Kyung ; Kim, Bo Mi ; Chu, Howard ; Lee, Hee Ra ; Kim, Hye Li ; Kim, Ji Hyung ; Fu, Xiujun ; Hyun, Young-Min ; Yun, Ki Na ; Kim, Jin Young ; Lee, Dong Won ; Song, Seung Yong ; Lin, Charles P. ; Clark, Rachael A. ; Lee, Kwang Hoon ; Kupper, Thomas S. ; Park, Chang Ook</creatorcontrib><description>Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD).
We aimed to investigate the role of NKT cells in AD development, especially in skin.
Global proteomic and transcriptomic analyses were performed by using skin and blood from human healthy–controls and patients with AD. Levels of CXCR4 and CXCL12 expression in skin NKT cells were analyzed in human AD and mouse AD models. By using parabiosis and intravital imaging, the role of skin CXCR4+ NKT cells was further evaluated in models of mice with AD by using CXCR4–conditionally deficient or CXCL12 transgenic mice.
CXCR4 and its cognate ligand CXCL12 were significantly upregulated in the skin of humans with AD by global transcriptomic and proteomic analyses. CXCR4+ NKT cells were enriched in AD skin, and their levels were consistently elevated in our models of mice with AD. Allergen-induced NKT cells participate in cutaneous allergic inflammation. Similar to tissue-resident memory T cells, the predominant skin NKT cells were CXCR4+ and CD69+. Skin-resident NKT cells uniquely expressed CXCR4, unlike NKT cells in the liver, spleen, and lymph nodes. Skin fibroblasts were the main source of CXCL12. CXCR4+ NKT cells preferentially trafficked to CXCL12-rich areas, forming an enriched CXCR4+ tissue-resident NKT cells/CXCL12+ cell cluster that developed in acute and chronic allergic inflammation in our models of mice with AD.
CXCR4+ tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.
[Display omitted]</description><identifier>ISSN: 0091-6749</identifier><identifier>EISSN: 1097-6825</identifier><identifier>DOI: 10.1016/j.jaci.2020.11.049</identifier><identifier>PMID: 33516870</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adaptive immunity ; Allergens ; Animal models ; Animals ; Atopic dermatitis ; CD69 antigen ; Chemokine CXCL12 - genetics ; Chemokine CXCL12 - immunology ; Chemokines ; CXCL12 ; CXCL12 protein ; CXCR4 ; CXCR4 protein ; Dermatitis ; Dermatitis, Atopic - genetics ; Dermatitis, Atopic - immunology ; Eczema ; Female ; Fibroblasts ; Gene Expression Profiling ; Hepatocytes ; Humans ; Hypersensitivity ; Immunological memory ; Inflammation ; Ligands ; Lymph nodes ; Lymphocytes ; Lymphocytes T ; Memory cells ; Mice ; Microscopy ; Natural killer cells ; natural killer T cells ; Natural Killer T-Cells - immunology ; Parabiosis ; Principal components analysis ; Proteins ; Proteomics ; Receptors, CXCR4 - genetics ; Receptors, CXCR4 - immunology ; Skin ; Skin - immunology ; Skin diseases ; Software ; Spleen ; Surgery ; thymic stromal lymphopoietin ; tissue-resident memory T cells ; Transgenic mice ; TRM cells</subject><ispartof>Journal of allergy and clinical immunology, 2021-05, Vol.147 (5), p.1764-1777</ispartof><rights>2021 American Academy of Allergy, Asthma & Immunology</rights><rights>Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.</rights><rights>2021. American Academy of Allergy, Asthma & Immunology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-f38ddd9aed56ddc5bb2983d5414c798b57b4b5b5d7efa4d9f1afc3b9c628d9e23</citedby><cites>FETCH-LOGICAL-c483t-f38ddd9aed56ddc5bb2983d5414c798b57b4b5b5d7efa4d9f1afc3b9c628d9e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S009167492100097X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33516870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, ZhengWang</creatorcontrib><creatorcontrib>Kim, Ji Hye</creatorcontrib><creatorcontrib>Kim, Seo Hyeong</creatorcontrib><creatorcontrib>Kim, Hye Ran</creatorcontrib><creatorcontrib>Zhang, KeLun</creatorcontrib><creatorcontrib>Pan, Youdong</creatorcontrib><creatorcontrib>Ko, Min Kyung</creatorcontrib><creatorcontrib>Kim, Bo Mi</creatorcontrib><creatorcontrib>Chu, Howard</creatorcontrib><creatorcontrib>Lee, Hee Ra</creatorcontrib><creatorcontrib>Kim, Hye Li</creatorcontrib><creatorcontrib>Kim, Ji Hyung</creatorcontrib><creatorcontrib>Fu, Xiujun</creatorcontrib><creatorcontrib>Hyun, Young-Min</creatorcontrib><creatorcontrib>Yun, Ki Na</creatorcontrib><creatorcontrib>Kim, Jin Young</creatorcontrib><creatorcontrib>Lee, Dong Won</creatorcontrib><creatorcontrib>Song, Seung Yong</creatorcontrib><creatorcontrib>Lin, Charles P.</creatorcontrib><creatorcontrib>Clark, Rachael A.</creatorcontrib><creatorcontrib>Lee, Kwang Hoon</creatorcontrib><creatorcontrib>Kupper, Thomas S.</creatorcontrib><creatorcontrib>Park, Chang Ook</creatorcontrib><title>Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis</title><title>Journal of allergy and clinical immunology</title><addtitle>J Allergy Clin Immunol</addtitle><description>Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD).
We aimed to investigate the role of NKT cells in AD development, especially in skin.
Global proteomic and transcriptomic analyses were performed by using skin and blood from human healthy–controls and patients with AD. Levels of CXCR4 and CXCL12 expression in skin NKT cells were analyzed in human AD and mouse AD models. By using parabiosis and intravital imaging, the role of skin CXCR4+ NKT cells was further evaluated in models of mice with AD by using CXCR4–conditionally deficient or CXCL12 transgenic mice.
CXCR4 and its cognate ligand CXCL12 were significantly upregulated in the skin of humans with AD by global transcriptomic and proteomic analyses. CXCR4+ NKT cells were enriched in AD skin, and their levels were consistently elevated in our models of mice with AD. Allergen-induced NKT cells participate in cutaneous allergic inflammation. Similar to tissue-resident memory T cells, the predominant skin NKT cells were CXCR4+ and CD69+. Skin-resident NKT cells uniquely expressed CXCR4, unlike NKT cells in the liver, spleen, and lymph nodes. Skin fibroblasts were the main source of CXCL12. CXCR4+ NKT cells preferentially trafficked to CXCL12-rich areas, forming an enriched CXCR4+ tissue-resident NKT cells/CXCL12+ cell cluster that developed in acute and chronic allergic inflammation in our models of mice with AD.
CXCR4+ tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.
[Display omitted]</description><subject>Adaptive immunity</subject><subject>Allergens</subject><subject>Animal models</subject><subject>Animals</subject><subject>Atopic dermatitis</subject><subject>CD69 antigen</subject><subject>Chemokine CXCL12 - genetics</subject><subject>Chemokine CXCL12 - immunology</subject><subject>Chemokines</subject><subject>CXCL12</subject><subject>CXCL12 protein</subject><subject>CXCR4</subject><subject>CXCR4 protein</subject><subject>Dermatitis</subject><subject>Dermatitis, Atopic - genetics</subject><subject>Dermatitis, Atopic - immunology</subject><subject>Eczema</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Gene Expression Profiling</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Hypersensitivity</subject><subject>Immunological memory</subject><subject>Inflammation</subject><subject>Ligands</subject><subject>Lymph nodes</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Memory cells</subject><subject>Mice</subject><subject>Microscopy</subject><subject>Natural killer cells</subject><subject>natural killer T cells</subject><subject>Natural Killer T-Cells - immunology</subject><subject>Parabiosis</subject><subject>Principal components analysis</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Receptors, CXCR4 - genetics</subject><subject>Receptors, CXCR4 - immunology</subject><subject>Skin</subject><subject>Skin - immunology</subject><subject>Skin diseases</subject><subject>Software</subject><subject>Spleen</subject><subject>Surgery</subject><subject>thymic stromal lymphopoietin</subject><subject>tissue-resident memory T cells</subject><subject>Transgenic mice</subject><subject>TRM cells</subject><issn>0091-6749</issn><issn>1097-6825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU9rFTEUxYMo9rX6BVzIgBs388zfmQREKEVroeCi7TpkkjttpjOZMckU_PbN8GpRF65CTn73kHMPQu8I3hNMmk_DfjDW7ymmRSB7zNULtCNYtXUjqXiJdhgrUjctV0foOKUBlzuT6jU6YkyQRrZ4h-6u7n2oIyTvIOQqmLxGM1b3fhwhVteVhXFM1WJi9tYvJkPlQ2XXbALMa6rMht16W9R-NNNksp_Dhpg8L0V2EDct-_QGverNmODt03mCbr59vT77Xl_-OL84O72sLZcs1z2TzjllwInGOSu6jirJnOCE21bJTrQd70QnXAu94U71xPSWdco2VDoFlJ2gLwffZe0mcLakKoH0Ev1k4i89G6__fgn-Tt_OD1rRlkqyGXx8MojzzxVS1pNP2xoOkTXlkhMhZcMK-uEfdJjXGEo8TQWlWDAhSaHogbJxTilC__wZgvVWpB70VqTeitSE6FJkGXr_Z4znkd_NFeDzAYCyzAcPUSfrIVhwPoLN2s3-f_6PADWypw</recordid><startdate>20210501</startdate><enddate>20210501</enddate><creator>Sun, ZhengWang</creator><creator>Kim, Ji Hye</creator><creator>Kim, Seo Hyeong</creator><creator>Kim, Hye Ran</creator><creator>Zhang, KeLun</creator><creator>Pan, Youdong</creator><creator>Ko, Min Kyung</creator><creator>Kim, Bo Mi</creator><creator>Chu, Howard</creator><creator>Lee, Hee Ra</creator><creator>Kim, Hye Li</creator><creator>Kim, Ji Hyung</creator><creator>Fu, Xiujun</creator><creator>Hyun, Young-Min</creator><creator>Yun, Ki Na</creator><creator>Kim, Jin Young</creator><creator>Lee, Dong Won</creator><creator>Song, Seung Yong</creator><creator>Lin, Charles P.</creator><creator>Clark, Rachael A.</creator><creator>Lee, Kwang Hoon</creator><creator>Kupper, Thomas S.</creator><creator>Park, Chang Ook</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210501</creationdate><title>Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis</title><author>Sun, ZhengWang ; Kim, Ji Hye ; Kim, Seo Hyeong ; Kim, Hye Ran ; Zhang, KeLun ; Pan, Youdong ; Ko, Min Kyung ; Kim, Bo Mi ; Chu, Howard ; Lee, Hee Ra ; Kim, Hye Li ; Kim, Ji Hyung ; Fu, Xiujun ; Hyun, Young-Min ; Yun, Ki Na ; Kim, Jin Young ; Lee, Dong Won ; Song, Seung Yong ; Lin, Charles P. ; Clark, Rachael A. ; Lee, Kwang Hoon ; Kupper, Thomas S. ; Park, Chang Ook</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-f38ddd9aed56ddc5bb2983d5414c798b57b4b5b5d7efa4d9f1afc3b9c628d9e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adaptive immunity</topic><topic>Allergens</topic><topic>Animal models</topic><topic>Animals</topic><topic>Atopic dermatitis</topic><topic>CD69 antigen</topic><topic>Chemokine CXCL12 - genetics</topic><topic>Chemokine CXCL12 - immunology</topic><topic>Chemokines</topic><topic>CXCL12</topic><topic>CXCL12 protein</topic><topic>CXCR4</topic><topic>CXCR4 protein</topic><topic>Dermatitis</topic><topic>Dermatitis, Atopic - genetics</topic><topic>Dermatitis, Atopic - immunology</topic><topic>Eczema</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Gene Expression Profiling</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Hypersensitivity</topic><topic>Immunological memory</topic><topic>Inflammation</topic><topic>Ligands</topic><topic>Lymph nodes</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Memory cells</topic><topic>Mice</topic><topic>Microscopy</topic><topic>Natural killer cells</topic><topic>natural killer T cells</topic><topic>Natural Killer T-Cells - immunology</topic><topic>Parabiosis</topic><topic>Principal components analysis</topic><topic>Proteins</topic><topic>Proteomics</topic><topic>Receptors, CXCR4 - genetics</topic><topic>Receptors, CXCR4 - immunology</topic><topic>Skin</topic><topic>Skin - immunology</topic><topic>Skin diseases</topic><topic>Software</topic><topic>Spleen</topic><topic>Surgery</topic><topic>thymic stromal lymphopoietin</topic><topic>tissue-resident memory T cells</topic><topic>Transgenic mice</topic><topic>TRM cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, ZhengWang</creatorcontrib><creatorcontrib>Kim, Ji Hye</creatorcontrib><creatorcontrib>Kim, Seo Hyeong</creatorcontrib><creatorcontrib>Kim, Hye Ran</creatorcontrib><creatorcontrib>Zhang, KeLun</creatorcontrib><creatorcontrib>Pan, Youdong</creatorcontrib><creatorcontrib>Ko, Min Kyung</creatorcontrib><creatorcontrib>Kim, Bo Mi</creatorcontrib><creatorcontrib>Chu, Howard</creatorcontrib><creatorcontrib>Lee, Hee Ra</creatorcontrib><creatorcontrib>Kim, Hye Li</creatorcontrib><creatorcontrib>Kim, Ji Hyung</creatorcontrib><creatorcontrib>Fu, Xiujun</creatorcontrib><creatorcontrib>Hyun, Young-Min</creatorcontrib><creatorcontrib>Yun, Ki Na</creatorcontrib><creatorcontrib>Kim, Jin Young</creatorcontrib><creatorcontrib>Lee, Dong Won</creatorcontrib><creatorcontrib>Song, Seung Yong</creatorcontrib><creatorcontrib>Lin, Charles P.</creatorcontrib><creatorcontrib>Clark, Rachael A.</creatorcontrib><creatorcontrib>Lee, Kwang Hoon</creatorcontrib><creatorcontrib>Kupper, Thomas S.</creatorcontrib><creatorcontrib>Park, Chang Ook</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of allergy and clinical immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, ZhengWang</au><au>Kim, Ji Hye</au><au>Kim, Seo Hyeong</au><au>Kim, Hye Ran</au><au>Zhang, KeLun</au><au>Pan, Youdong</au><au>Ko, Min Kyung</au><au>Kim, Bo Mi</au><au>Chu, Howard</au><au>Lee, Hee Ra</au><au>Kim, Hye Li</au><au>Kim, Ji Hyung</au><au>Fu, Xiujun</au><au>Hyun, Young-Min</au><au>Yun, Ki Na</au><au>Kim, Jin Young</au><au>Lee, Dong Won</au><au>Song, Seung Yong</au><au>Lin, Charles P.</au><au>Clark, Rachael A.</au><au>Lee, Kwang Hoon</au><au>Kupper, Thomas S.</au><au>Park, Chang Ook</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis</atitle><jtitle>Journal of allergy and clinical immunology</jtitle><addtitle>J Allergy Clin Immunol</addtitle><date>2021-05-01</date><risdate>2021</risdate><volume>147</volume><issue>5</issue><spage>1764</spage><epage>1777</epage><pages>1764-1777</pages><issn>0091-6749</issn><eissn>1097-6825</eissn><abstract>Natural killer T (NKT) cells are unconventional T cells that bridge innate and adaptive immunity. NKT cells have been implicated in the development of atopic dermatitis (AD).
We aimed to investigate the role of NKT cells in AD development, especially in skin.
Global proteomic and transcriptomic analyses were performed by using skin and blood from human healthy–controls and patients with AD. Levels of CXCR4 and CXCL12 expression in skin NKT cells were analyzed in human AD and mouse AD models. By using parabiosis and intravital imaging, the role of skin CXCR4+ NKT cells was further evaluated in models of mice with AD by using CXCR4–conditionally deficient or CXCL12 transgenic mice.
CXCR4 and its cognate ligand CXCL12 were significantly upregulated in the skin of humans with AD by global transcriptomic and proteomic analyses. CXCR4+ NKT cells were enriched in AD skin, and their levels were consistently elevated in our models of mice with AD. Allergen-induced NKT cells participate in cutaneous allergic inflammation. Similar to tissue-resident memory T cells, the predominant skin NKT cells were CXCR4+ and CD69+. Skin-resident NKT cells uniquely expressed CXCR4, unlike NKT cells in the liver, spleen, and lymph nodes. Skin fibroblasts were the main source of CXCL12. CXCR4+ NKT cells preferentially trafficked to CXCL12-rich areas, forming an enriched CXCR4+ tissue-resident NKT cells/CXCL12+ cell cluster that developed in acute and chronic allergic inflammation in our models of mice with AD.
CXCR4+ tissue-resident NKT cells may form a niche that contributes to AD, in which CXCL12 is highly expressed.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33516870</pmid><doi>10.1016/j.jaci.2020.11.049</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of allergy and clinical immunology, 2021-05, Vol.147 (5), p.1764-1777 |
| issn | 0091-6749 1097-6825 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adaptive immunity Allergens Animal models Animals Atopic dermatitis CD69 antigen Chemokine CXCL12 - genetics Chemokine CXCL12 - immunology Chemokines CXCL12 CXCL12 protein CXCR4 CXCR4 protein Dermatitis Dermatitis, Atopic - genetics Dermatitis, Atopic - immunology Eczema Female Fibroblasts Gene Expression Profiling Hepatocytes Humans Hypersensitivity Immunological memory Inflammation Ligands Lymph nodes Lymphocytes Lymphocytes T Memory cells Mice Microscopy Natural killer cells natural killer T cells Natural Killer T-Cells - immunology Parabiosis Principal components analysis Proteins Proteomics Receptors, CXCR4 - genetics Receptors, CXCR4 - immunology Skin Skin - immunology Skin diseases Software Spleen Surgery thymic stromal lymphopoietin tissue-resident memory T cells Transgenic mice TRM cells |
| title | Skin-resident natural killer T cells participate in cutaneous allergic inflammation in atopic dermatitis |
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