Aradi, Petra and Kovács, Gábor and Kemecsei, Éva and Molnár, Kornél and Sági, Stella Márta and Horváth, Zalán and Mehrara, Babak J. and Kataru, Raghu P. and Jakus, Zoltán (2024) Lymphatic-dependent modulation of the sensitization and elicitation phases of contact hypersensitivity. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2024. pp. 2240-2254. ISSN 0022-202X
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Abstract
Allergic contact dermatitis is a common inflammatory skin disease comprising 2 phases. During sensitization, immune cells are activated by exposure to various allergens, whereas repeated antigen exposure induces local inflammation during elicitation. In this study, we utilized mouse models lacking lymphatics in different skin regions to characterize the role of lymphatics separately in the 2 phases, using contact hypersensitivity as a model of human allergic inflammatory skin diseases. Lymphatic-deficient mice exhibited no major difference to single antigen exposure compared to controls. However, mice lacking lymphatics in both phases displayed reduced inflammation after repeated antigen exposure. Similarly, diminished immune response was observed in mice lacking lymphatics only in sensitization, whereas the absence of lymphatics only in the elicitation phase resulted in a more pronounced inflammatory immune response. This exaggerated inflammation is driven by neutrophils impacting regulatory T cell number. Collectively, our results demonstrate that skin lymphatics play an important but distinct role in the 2 phases of contact hypersensitivity. During sensitization, lymphatics contribute to the development of the antigen-specific immunization, whereas in elicitation, they moderate the inflammatory response and leukocyte infiltration in a neutrophil-dependent manner. These findings underscore the need for novel therapeutic strategies targeting the lymphatics in the context of allergic skin diseases.
| Item Type: | Article |
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| Additional Information: | Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States Export Date: 12 September 2024 CODEN: JIDEA Correspondence Address: Jakus, Z.; Department of Physiology, Tűzoltó utca 37-47, Hungary; email: jakus.zoltan@semmelweis.hu Funding details: European Commission, EC Funding details: Magyar Tudományos Akadémia, MTA, BO/00898/22 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, TKP2021-EGA-24, NVKP_16-1-2016-0039, TKP2021-EGA-29, K139165 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, UNKP-23-5-SE-10 Funding details: Magyarország Kormánya, EFOP-3.6.3-VEKOP-16-2017-00009, VEKOP-2.3.3-15-2016-00006 Funding text 1: We thank V. N\\u00E9meth, E. Marink\\u00E1s, D. Csengel for excellent technical assistance and Young-Kwon Hong for Prox1 GFP mice. This work was supported by the National Research, Development and Innovation Office (K139165, TKP2021-EGA-29, TKP2021-EGA-24, NVKP_16-1-2016-0039), the European Union and the Hungarian Government (VEKOP-2.3.2-16-2016-00002, VEKOP-2.3.3-15-2016-00006, EFOP-3.6.3-VEKOP-16-2017-00009). Z.J. is a recipient of the J\\u00E1nos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00898/22) and the New National Excellence Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund (UNKP-23-5-SE-10). K.M. was supported by the National Academy of Scientist Education Program of the National Biomedical Foundation. |
| Uncontrolled Keywords: | Contact hypersensitivity, Inflammation, Mouse models, Neutrophil granulocytes, Skin lymphatics |
| Subjects: | B Philosophy. Psychology. Religion / filozófia, pszichológia, vallás > BF Psychology / lélektan R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában R Medicine / orvostudomány > RM Therapeutics. Pharmacology / terápia, gyógyszertan |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 19 Sep 2024 13:30 |
| Last Modified: | 19 Sep 2024 13:30 |
| URI: | https://real.mtak.hu/id/eprint/205286 |
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