Possible involvement of the interleukin-15 and interleukin-15 receptor system in a heightened state of lamina propria B cell activation and differentiation in patients with inflammatory bowel disease.
BACKGROUND
We investigated the possible roles of the interleukin (IL)-15 and IL-15 receptor (IL-15R) system in a heightened state of B-cell activation and differentiation in intestinal mucosa with inflammatory bowel disease (IBD).


METHODS
The expression of IL-15 and IL-15Ralpha mRNA and protein in inflamed colonic mucosal tissues with IBD, and in control tissues was examined by reverse transcriptase-polymerase chain reaction and immunohistological methods. The effects of recombinant (r)IL-15 on the expression of IL-15Ralpha on lamina propria B cells and the production of immunoglobulin G (IgG) were analyzed in vitro, using lamina propria mononuclear cells (LPMCs) isolated from control tissues.


RESULTS
The intensity of IL-15 and IL-15Ralpha mRNA was greater in the mucosal tissues of patients with IBD, especially in those of patients with ulcerative colitis (UC), than in control tissues. Compared to control tissues, mononuclear cells positive for IL-15Ralpha protein were observed in greater proportions in tissue sections from patients with IBD, especially in those from patients with UC, where IL-15Ralpha protein was localized to CD20-positive B cells to a significant degree. There were increases in the proportions of IL-15Ralpha-positive B cells and IgG-producing cells in rIL-15- or rCD40L-stimulated cultures of LPMCs, with stimulatory effects being greater in the presence of their combination.


CONCLUSIONS
These data suggest that the IL-15 and IL-15R system may play important roles in the activation and differentiation of lamina propria B cells in patients with IBD, especially in those with UC.
Nishiwaki
Tsuyoshi
T
Department of Therapeutic Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Ina
Kenji
K
Goto
Hidemi
H
Watanabe
Osamu
O
Tsuzuki
Tomoyuki
T
Furuta
Ryuichi
R
Ando
Takafumi
T
Hibi
Kenji
K
Kusugami
Kazuo
K
D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000503:physiopathology*; D003424:Crohn Disease / Q000378:metabolism / Q000503:physiopathology*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D018613:Microscopy, Confocal; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology
D019409:Interleukin-15; D018123:Receptors, Interleukin