Production of IL-31 in CD45RO+CLA+H4R+ T Cells in Atopic Dermatitis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Human Tissue Samples
2.2. Immunofluorescence for Skin Tissue
2.3. AD Patient Recruitment and Blood Samples
2.4. Isolation of PBMCs from whole blood
2.5. Fluorescence-Activated Cell Sorting
2.6. Immunofluorescence for PBMC
2.7. Enzyme-Linked Immunosorbent Assay for IL-31
2.8. Statistical Analysis
3. Results
3.1. Co-Localization of H4R and IL-31 in Lesional AD Skin
3.2. Characteristics of AD Patients
3.3. Comparison of CD45RO+CLA+H4R+ T Cells in Patients with AD and Healthy Controls
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
4MH | 4-methylhistamine dihydrochloride |
AD | atopic dermatitis |
BSA | bovine serum albumin |
CLA | cutaneous lymphocyte-associated antigen |
FACS | fluorescence-activated cell sorting |
H1R | histamine-1-receptor |
H4R | histamine-4-receptor |
IF | immunofluorescence |
IL | interleukin |
JAK | Janus kinase |
PBMC | peripheral blood mononuclear cell |
SEB | staphylococcal enterotoxin B |
TSLP | thymic stromal lymphopoietin |
References
- Dillon, S.R.; Sprecher, C.; Hammond, A.; Bilsborough, J.; Rosenfeld-Franklin, M.; Presnell, S.R.; Haugen, H.S.; Maurer, M.; Harder, B.; Johnston, J.; et al. Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nat. Immunol. 2004, 5, 752–760. [Google Scholar] [CrossRef] [PubMed]
- Bagci, I.S.; Ruzicka, T. IL-31: A new key player in dermatology and beyond. J. Allergy Clin. Immunol. 2018, 141, 858–866. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ezzat, M.H.; Hasan, Z.E.; Shaheen, K.Y. Serum measurement of interleukin-31 (IL-31) in paediatric atopic dermatitis: Elevated levels correlate with severity scoring. J. Eur. Acad. Dermatol. Venereol. 2011, 25, 334–339. [Google Scholar] [CrossRef] [PubMed]
- Ruzicka, T.; Hanifin, J.M.; Furue, M.; Pulka, G.; Mlynarczyk, I.; Wollenberg, A.; Galus, R.; Etoh, T.; Mihara, R.; Yoshida, H.; et al. Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis. N. Engl. J. Med. 2017, 376, 826–835. [Google Scholar] [CrossRef] [PubMed]
- Bilsborough, J.; Leung, D.Y.; Maurer, M.; Howell, M.; Boguniewicz, M.; Yao, L.; Storey, H.; LeCiel, C.; Harder, B.; Gross, J.A. IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis. J. Allergy Clin. Immunol. 2006, 117, 418–425. [Google Scholar] [CrossRef]
- Stott, B.; Lavender, P.; Lehmann, S.; Pennino, D.; Durham, S.; Schmidt-Weber, C.B. Human IL-31 is induced by IL-4 and promotes TH2-driven inflammation. J. Allergy Clin. Immunol. 2013, 132, 446–454 e445. [Google Scholar] [CrossRef] [PubMed]
- Cevikbas, F.; Wang, X.; Akiyama, T.; Kempkes, C.; Savinko, T.; Antal, A.; Kukova, G.; Buhl, T.; Ikoma, A.; Buddenkotte, J.; et al. A sensory neuron-expressed IL-31 receptor mediates T helper cell-dependent itch: Involvement of TRPV1 and TRPA1. J. Allergy Clin. Immunol. 2014, 133, 448–460. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Maier, E.; Werner, D.; Duschl, A.; Bohle, B.; Horejs-Hoeck, J. Human Th2 but not Th9 cells release IL-31 in a STAT6/NF-kappaB-dependent way. J. Immunol. 2014, 193, 645–654. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cornelissen, C.; Brans, R.; Czaja, K.; Skazik, C.; Marquardt, Y.; Zwadlo-Klarwasser, G.; Kim, A.; Bickers, D.R.; Luscher-Firzlaff, J.; Luscher, B.; et al. Ultraviolet B radiation and reactive oxygen species modulate interleukin-31 expression in T lymphocytes, monocytes and dendritic cells. Br. J. Dermatol. 2011, 165, 966–975. [Google Scholar] [CrossRef]
- Thurmond, R.L.; Gelfand, E.W.; Dunford, P.J. The role of histamine H1 and H4 receptors in allergic inflammation: The search for new antihistamines. Nat. Rev. Drug. Discov. 2008, 7, 41–53. [Google Scholar] [CrossRef]
- Gutzmer, R.; Mommert, S.; Gschwandtner, M.; Zwingmann, K.; Stark, H.; Werfel, T. The histamine H4 receptor is functionally expressed on T(H)2 cells. J. Allergy Clin. Immunol. 2009, 123, 619–625. [Google Scholar] [CrossRef]
- Ohsawa, Y.; Hirasawa, N. The role of histamine H1 and H4 receptors in AD. Allergol. Int. 2014, 63, 10. [Google Scholar] [CrossRef] [Green Version]
- Raap, U.; Gehring, M.; Kleiner, S.; Rudrich, U.; Eiz-Vesper, B.; Haas, H.; Kapp, A.; Gibbs, B.F. Human basophils are a source of—and are differentially activated by—IL-31. Clin. Exp. Allergy 2017, 47, 499–508. [Google Scholar] [CrossRef]
- Feld, M.; Garcia, R.; Buddenkotte, J.; Katayama, S.; Lewis, K.; Muirhead, G.; Hevezi, P.; Plesser, K.; Schrumpf, H.; Krjutskov, K.; et al. The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. J. Allergy Clin. Immunol. 2016, 138, 500–508 e524. [Google Scholar] [CrossRef] [Green Version]
- Park, K.; Park, J.H.; Yang, W.J.; Lee, J.J.; Song, M.J.; Kim, H.P. Transcriptional activation of the IL31 gene by NFAT and STAT6. J. Leukoc. Biol. 2012, 91, 245–257. [Google Scholar] [CrossRef]
- Jutel, M.; Watanabe, T.; Akdis, M.; Blaser, K.; Akdis, C.A. Immune regulation by histamine. Curr. Opin. Immunol. 2002, 14, 6. [Google Scholar] [CrossRef]
- Werfel, T.; Layton, G.; Yeadon, M.; Whitlock, L.; Osterloh, I.; Jimenez, P.; Liu, W.; Lynch, V.; Asher, A.; Tsianakas, A.; et al. Efficacy and safety of the histamine H4 receptor antagonist ZPL-3893787 in patients with atopic dermatitis. J. Allergy Clin. Immunol. 2019, 143, 1830–1837e1834. [Google Scholar] [CrossRef]
- Rossbach, K.; Wendorff, S.; Sander, K.; Stark, H.; Gutzmer, R.; Werfel, T.; Kietzmann, M.; Baumer, W. Histamine H4 receptor antagonism reduces hapten-induced scratching behaviour but not inflammation. Exp. Dermatol. 2009, 18, 57–63. [Google Scholar] [CrossRef]
- Seike, M.; Furuya, K.; Omura, M.; Hamada-Watanabe, K.; Matsushita, A.; Ohtsu, H. Histamine H(4) receptor antagonist ameliorates chronic allergic contact dermatitis induced by repeated challenge. Allergy 2010, 65, 319–326. [Google Scholar] [CrossRef]
- Dunford, P.J.; Williams, K.N.; Desai, P.J.; Karlsson, L.; McQueen, D.; Thurmond, R.L. Histamine H4 receptor antagonists are superior to traditional antihistamines in the attenuation of experimental pruritus. J. Allergy Clin. Immunol. 2007, 119, 176–183. [Google Scholar] [CrossRef]
- Murata, Y.; Song, M.; Kikuchi, H.; Hisamichi, K.; Xu, X.L.; Greenspan, A.; Kato, M.; Chiou, C.F.; Kato, T.; Guzzo, C.; et al. Phase 2a, randomized, double-blind, placebo-controlled, multicenter, parallel-group study of a H4 R-antagonist (JNJ-39758979) in Japanese adults with moderate atopic dermatitis. J. Dermatol. 2015, 42, 129–139. [Google Scholar] [CrossRef] [PubMed]
- Kollmeier, A.; Francke, K.; Chen, B.; Dunford, P.J.; Greenspan, A.J.; Xia, Y.; Xu, X.L.; Zhou, B.; Thurmond, R.L. The histamine H(4) receptor antagonist, JNJ 39758979, is effective in reducing histamine-induced pruritus in a randomized clinical study in healthy subjects. J. Pharmacol. Exp. Ther. 2014, 350, 181–187. [Google Scholar] [CrossRef] [PubMed]
- Dijkstra, D.; Stark, H.; Chazot, P.L.; Shenton, F.C.; Leurs, R.; Werfel, T.; Gutzmer, R. Human inflammatory dendritic epidermal cells express a functional histamine H4 receptor. J. Investig. Dermatol. 2008, 128, 1696–1703. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gutzmer, R.; Diestel, C.; Mommert, S.; Kother, B.; Stark, H.; Wittmann, M.; Werfel, T. Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. J. Immunol. 2005, 174, 5224–5232. [Google Scholar] [CrossRef]
- Glatzer, F.; Gschwandtner, M.; Ehling, S.; Rossbach, K.; Janik, K.; Klos, A.; Baumer, W.; Kietzmann, M.; Werfel, T.; Gutzmer, R. Histamine induces proliferation in keratinocytes from patients with atopic dermatitis through the histamine 4 receptor. J. Allergy Clin. Immunol. 2013, 132, 1358–1367. [Google Scholar] [CrossRef] [Green Version]
- Schaper, K.; Rossbach, K.; Kother, B.; Stark, H.; Kietzmann, M.; Werfel, T.; Gutzmer, R. Stimulation of the histamine 4 receptor upregulates thymic stromal lymphopoietin (TSLP) in human and murine keratinocytes. Pharmacol. Res. 2016, 113, 209–215. [Google Scholar] [CrossRef]
- Renert-Yuval, Y.; Guttman-Yassky, E. New treatments for atopic dermatitis targeting beyond IL-4/IL-13 cytokines. Ann. Allergy Asthma. Immunol. 2020, 124, 28–35. [Google Scholar] [CrossRef] [Green Version]
- Thaçi, D.; Simpson, E.L.; Beck, L.A.; Bieber, T.; Blauvelt, A.; Papp, K.; Soong, W.; Worm, M.; Szepietowski, J.C.; Sofen, H.; et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: A randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet 2016, 387, 40–52. [Google Scholar] [CrossRef]
- Simpson, E.L.; Bieber, T.; Guttman-Yassky, E.; Beck, L.A.; Blauvelt, A.; Cork, M.J.; Silverberg, J.I.; Deleuran, M.; Kataoka, Y.; Lacour, J.P.; et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N. Engl. J. Med. 2016, 375, 2335–2348. [Google Scholar] [CrossRef]
- Blauvelt, A.; de Bruin-Weller, M.; Gooderham, M.; Cather, J.C.; Weisman, J.; Pariser, D.; Simpson, E.L.; Papp, K.A.; Hong, H.C.-H.; Rubel, D.; et al. Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): A 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet 2017, 389, 2287–2303. [Google Scholar] [CrossRef]
- Guttman-Yassky, E.; Silverberg, J.I.; Nemoto, O.; Forman, S.B.; Wilke, A.; Prescilla, R.; de la Pena, A.; Nunes, F.P.; Janes, J.; Gamalo, M.; et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J. Am. Acad. Dermatol. 2019, 80, 913–921 e919. [Google Scholar] [CrossRef]
- Bissonnette, R.; Maari, C.; Forman, S.; Bhatia, N.; Lee, M.; Fowler, J.; Tyring, S.; Pariser, D.; Sofen, H.; Dhawan, S.; et al. The oral Janus kinase/spleen tyrosine kinase inhibitor ASN002 demonstrates efficacy and improves associated systemic inflammation in patients with moderate-to-severe atopic dermatitis: Results from a randomized double-blind placebo-controlled study. Br. J. Dermatol. 2019, 181, 733–742. [Google Scholar] [CrossRef] [Green Version]
- Guttman-Yassky, E.; Pavel, A.B.; Zhou, L.; Estrada, Y.D.; Zhang, N.; Xu, H.; Peng, X.; Wen, H.C.; Govas, P.; Gudi, G.; et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J. Allergy Clin. Immunol. 2019, 144, 482–493e487. [Google Scholar] [CrossRef] [Green Version]
- Guttman-Yassky, E.; Brunner, P.M.; Neumann, A.U.; Khattri, S.; Pavel, A.B.; Malik, K.; Singer, G.K.; Baum, D.; Gilleaudeau, P.; Sullivan-Whalen, M.; et al. Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial. J. Am. Acad. Dermatol. 2018, 78, 872–881 e876. [Google Scholar] [CrossRef] [Green Version]
- Czarnowicki, T.; He, H.; Krueger, J.G.; Guttman-Yassky, E. Atopic dermatitis endotypes and implications for targeted therapeutics. J. Allergy Clin. Immunol. 2019, 143, 1–11. [Google Scholar] [CrossRef]
Target | Primary Antibody | Secondary Antibody | |||
---|---|---|---|---|---|
Clonality | Host | Fluorophore | Reactivity | Host | |
CD3 | Monoclonal | Human | Alexa fluor® 405 | Conjugated | |
CD45RO | Monoclonal | Mouse | Alexa fluor® 488 | Mouse | Goat |
CLA | Monoclonal | Rat | Allophycocyanin | Rat | Goat |
H4R | Polyclonal | Rabbit | PE-cyanine 5.5 | Rabbit | Goat |
Case ID | Age | Sex | IgE (IU/mL) | Biopsy Site |
---|---|---|---|---|
1 | 5 | M | NA | Back |
2 | 23 | F | NA | Back |
3 | 24 | F | 2280 | Thigh |
4 | 37 | F | 2153 | Lowe leg |
5 | 62 | M | 3412 | Face |
Total | 30.2 ± 21.1 | 2615 ± 693 |
Case ID | Age | Sex | Eosinophils (%) | IgE (IU/mL) | ECP (ng/mL) | SCORAD |
---|---|---|---|---|---|---|
AD1 | 20 | M | 8.2 | NA | NA | 54.6 |
AD2 | 19 | M | 2.2 | 1284 | 26.7 | 39.5 |
AD3 | 36 | F | 10.1 | 2346 | 46.5 | 35.0 |
AD4 | 20 | M | 7.5 | 5369 | 114 | 49.1 |
AD5 | 35 | F | 6.9 | 1968 | 122 | 35.9 |
AD6 | 26 | M | 10.9 | 13,600 | NA | 56.5 |
AD7 | 24 | F | 7.0 | 3349 | 114 | 51.5 |
AD8 | 25 | M | 13.0 | 5991 | NA | 77.6 |
Total | 25.6 ± 6.6 | 8.2 ± 3.2 | 4843.9 ± 4236.3 | 84.6 ± 44.5 | 50.0 ± 14.0 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bang, C.H.; Song, J.Y.; Song, Y.M.; Lee, J.H.; Park, Y.M.; Lee, J.Y. Production of IL-31 in CD45RO+CLA+H4R+ T Cells in Atopic Dermatitis. J. Clin. Med. 2021, 10, 1976. https://doi.org/10.3390/jcm10091976
Bang CH, Song JY, Song YM, Lee JH, Park YM, Lee JY. Production of IL-31 in CD45RO+CLA+H4R+ T Cells in Atopic Dermatitis. Journal of Clinical Medicine. 2021; 10(9):1976. https://doi.org/10.3390/jcm10091976
Chicago/Turabian StyleBang, Chul Hwan, Ji Young Song, Yu Mee Song, Ji Hyun Lee, Young Min Park, and Jun Young Lee. 2021. "Production of IL-31 in CD45RO+CLA+H4R+ T Cells in Atopic Dermatitis" Journal of Clinical Medicine 10, no. 9: 1976. https://doi.org/10.3390/jcm10091976