IL-2 regulates CD103 expression on CD4+ T cells in Scurfy mice that display both CD103-dependent and independent inflammation.
Scurfy (Sf) mice lack CD4(+)Foxp3(+) regulatory T cells and develop fatal multiorgan inflammation (MOI) mediated by CD4(+) T cells. Introducing Il2(-/-) gene into Sf mice (Sf.Il2(-/-)) inhibited inflammation in skin and lung. As a major integrin receptor for the organs, we compared CD103 expression on the CD4(+) T cells of B6, Il2(-/-), Sf, and Sf.Il2(-/-) mice. CD103(+)CD4(+) T cells, but not CD8(+) T cells or CD11c(+) dendritic cells, were significantly up-regulated only in Sf mice, indicating Il2(-/-) dominantly and specifically inhibited CD103 up-regulation in Sf CD4(+) T cells. In addition, CD4(+)Foxp3(+) regulatory T cell CD103 expression was not reduced in Il2(-/-) mice. Introducing CD103(-/-) into Sf mice inhibited inflammation in skin and lung as compared with age-matched Sf mice, but they died at approximately 7 wk old with inflammation developed in skin, lungs, and colon, demonstrating fatal MOI induced by CD103-independent mechanism. Transfer of Sf CD4(+) T cells induced MOI more rapidly than CD103(-)CD4(+) T cells, indicating the presence of CD103-dependent mechanism for inflammation. In vitro stimulation with anti-CD3 plus anti-CD28 beads confirmed that CD103 induction in the CD4(+)Foxp3(-) T cells in Il2(-/-) and Sf.Il2(-/-) is defective and cannot be restored by rIL-2 or rIL-15. The data indicate that IL-2 is required for optimal CD103 induction on CD4(+) T cells in Sf mice and this effect contributes to inflammation in an organ-specific manner. IL-2 also has additional roles because the protection of skin and lung inflammation in Sf.Il2(-/-), but not Sf.CD103(-/-) mice is lifelong and Sf.Il2(-/-) mice have longer lifespan than Sf.CD103(-/-) mice.
Sharma
Rahul
R
Center for Immunity, Inflammation, and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Sung
Sun-sang Joe
SS
Abaya
Christian E
CE
Ju
Angela Chiao-Ying
AC
Fu
Shu Man
SM
Ju
Shyr-Te
ST
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000637:transplantation; D002423:Cause of Death; D007249:Inflammation / Q000209:etiology* / Q000401:mortality; D039001:Integrin alpha Chains / Q000235:genetics* / Q000502:physiology; D007376:Interleukin-2 / Q000172:deficiency / Q000502:physiology*; D008136:Longevity; D008168:Lung / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D012867:Skin / Q000473:pathology; D050378:T-Lymphocytes, Regulatory; D015533:Transcriptional Activation
D015703:Antigens, CD; D039001:Integrin alpha Chains; D007376:Interleukin-2; C091367:alpha E integrins