IL-36 receptor is expressed by human blood and intestinal T lymphocytes and is dose-dependently activated via IL-36β and induces CD4+ lymphocyte proliferation.
We show that IL-36R is expressed by T (CD4+ and CD8+) and B (CD19+) lymphocytes in human blood and also by CD4+ T lymphocytes in the intestinal lamina propria. IL-36R protein was mostly stored in the cytoplasm of CD4 lymphocytes and B cells, during steady state conditions and the greatest expression of IL-36R mRNA was measured in CD4+ (T helper) lymphocytes. IL-36 β, which functions via IL-36R induced rapid and significant (P<0.05) proliferation of CD4+ lymphocytes, within 48h. IL-36R expression was also maintained on the surface of circulating CD4+ lymphocytes which enter the intestinal lamina propria. In conclusion our study is the first to show that (1) all human blood lymphocytes express IL-36R; (2) IL-36R expression is maintained by circulating CD4+ lymphocytes which enter the intestinal lamina propria and (3) IL-36R/IL-36 β induces rapid CD4 lymphocyte proliferation. The possible significance of these results in the context of human disease is discussed.
School of Veterinary Medicine and Science, University of Nottingham, UK.
Rafael
R
Penha
School of Veterinary Medicine and Science, University of Nottingham, UK.
John
J
Higgins
School of Veterinary Medicine and Science, University of Nottingham, UK.
Shilla
S
Mutamba
School of Veterinary Medicine and Science, University of Nottingham, UK.
Paul
P
Barrow
The Institute of Infection, Immunity and Inflammation, University of Nottingham, UK.
Yashwant
Y
Mahida
School of Veterinary Medicine and Science, University of Nottingham, UK. Electronic address: n.foster@nottingham.ac.uk.
Neil
N
Foster
D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D012333:RNA, Messenger / Q000276:immunology; D018123:Receptors, Interleukin / Q000276:immunology
D012333:RNA, Messenger; D018123:Receptors, Interleukin; C571244:interleukin-36 receptor, human
Human; IL-36; IL-36R; Lymphocyte