IL-9 production by regulatory T cells recruits mast cells that are essential for regulatory T cell-induced immune suppression.
Both mast cells (MCs) and regulatory T cells (Tregs) have gained attention as immunosuppressive cell populations. To investigate a possible interaction, we used the Th1- and Th17-dependent model of nephrotoxic serum nephritis (NTS), in which both MCs and Tregs have been shown to play a protective role. Transfer of wild-type (wt) Tregs into wt recipients almost completely prevents development of NTS and leads to a profound increase of MCs in the renal draining lymph nodes (LNs). By contrast, transfer of wt Tregs into animals deficient in MCs, which are characterized by an exaggerated susceptibility to NTS, no longer exhibited protective effects. Blocking the pleiotropic cytokine IL-9, known to be involved in MC recruitment and proliferation, by means of a mAb in mice receiving Tregs abrogated protection from NTS. Moreover, transfer of IL-9-deficient Tregs also failed to protect from NTS. In the absence of Treg-derived IL-9, MCs fail to accumulate in the LNs, despite the fact that IL-9 deficiency does not alter the general suppressive activity of Tregs. In summary, to our knowledge, we provide the first direct in vivo evidence that the nephroprotective, anti-inflammatory effects of Tregs critically depend on IL-9-mediated attraction of MCs into kidney-draining LNs.
Division of Nephrology and Hypertension, Department of Internal Medicine IV, Medical University, Innsbruck, Austria.
Kathrin
K
Eller
Dominik
D
Wolf
Julia M
JM
Huber
Martin
M
Metz
Gert
G
Mayer
Andrew N J
AN
McKenzie
Marcus
M
Maurer
Alexander R
AR
Rosenkranz
Anna M
AM
Wolf
D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000172:deficiency / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009393:Nephritis / Q000276:immunology* / Q000473:pathology* / Q000517:prevention & control; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000637:transplantation
D018836:Inflammation Mediators; D016906:Interleukin-9