Expression of IL-1Rrp2 by human myelomonocytic cells is unique to DCs and facilitates DC maturation by IL-1F8 and IL-1F9

Eur J Immunol. 2012 Mar;42(3):607-17. doi: 10.1002/eji.201142035.

Abstract

We report for the first time that expression of the novel IL-1 cytokine receptor IL-1Rrp2 (IL-1R6) is unique to DCs within the human myelomonocytic lineage. IL-1Rrp2 was expressed by monocyte-derived dendritic cells (MDDCs) which was dose-dependently increased by IL-4 and correlated with increased numbers of differentiated MDDCs. Human plasmacytoid DCs also express IL-1Rrp2 but the receptor is not expressed by either myeloid DC type 1 (mDC1) or mDC2 cells. We also show that IL-1F8 or IL-1F9 cytokines, which signal through IL-1Rrp2, induce maturation of MDDCs, as measured by increased expression of HLA-DR and CD83 and decreased expression of CD1a. Furthermore, IL-1F8 stimulated increased CD40 and CD80 expression and IL-18 and IL-12 p70 production by MDDCs, which induced proliferation of IFN-γ-producing CD3(+) lymphocytes (indicative of inflammatory Th1 subsets). IL-1F8 and IL-1F2 were equipotent in their ability to stimulate IL-18 secretion from MDDCs but IL-1F8 was not as potent as IL-1F2 in stimulating secretion of IL-12p70 from MDDCs or inducing lymphocyte proliferation Therefore, IL-1Rrp2 expression by some DC subsets may have an important function in the human immune response in vivo via its role in differentiation of inflammatory Th1 lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / immunology
  • Antigens, CD1 / immunology
  • Cell Differentiation / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Flow Cytometry
  • HLA-DR Antigens / immunology
  • Humans
  • Immunoglobulins / immunology
  • Interleukin-1 / immunology*
  • Interleukin-18 Receptor alpha Subunit / biosynthesis*
  • Interleukin-18 Receptor alpha Subunit / genetics
  • Interleukin-18 Receptor alpha Subunit / immunology
  • Leukocytes, Mononuclear / immunology
  • Membrane Glycoproteins / immunology
  • Microscopy, Phase-Contrast
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Th1 Cells / immunology

Substances

  • Antigens, CD
  • Antigens, CD1
  • CD1a antigen
  • CD83 antigen
  • HLA-DR Antigens
  • IL18R1 protein, human
  • IL36B protein, human
  • IL36G protein, human
  • Immunoglobulins
  • Interleukin-1
  • Interleukin-18 Receptor alpha Subunit
  • Membrane Glycoproteins
  • RNA, Messenger