title: Interleukin-7 (IL-7) treatment accelerates neutrophil recruitment through gamma delta T-cell IL-17 production in a murine model of sepsis.
abstract: The sepsis syndrome represents an improper immune response to infection and is associated with unacceptably high rates of mortality and morbidity. The interactions between T cells and the innate immune system while combating sepsis are poorly understood. In this report, we observed that treatment with the potent, antiapoptotic cytokine interleukin-7 (IL-7) accelerated neutrophil recruitment and improved bacterial clearance. We first determined that T cells were necessary for the previously observed IL-7-mediated enhanced survival. Next, IL-7 increased Bcl-2 expression in T cells isolated from septic mice as early as 3 h following treatment. This treatment resulted in increased gamma interferon (IFN-γ) and IP-10 production within the septic peritoneum together with local and systemic increases of IL-17 in IL-7-treated mice. We further demonstrate that the increase in IL-17 was largely due to increased recruitment and production by γδ T cells, which express CXCR3. Consistent with increased IL-17 production, IL-7 treatment increased CXCL1/KC production, neutrophil recruitment, and bacterial clearance. Significantly, end-organ tissue injury was not significantly different between vehicle- and IL-7-treated mice. Collectively, these data illustrate that IL-7 can mediate the cross talk between Th1 and Th17 lymphocytes during sepsis such that neutrophil recruitment and bacterial clearance is improved while early tissue injury is not increased. All together, these observations may underlay novel potential therapeutic targets to improve the host immune response to sepsis.
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0558, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Kasten
authors.forename: Priya S
authors.initials: PS
authors.lastname: Prakash
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Unsinger
authors.forename: Holly S
authors.initials: HS
authors.lastname: Goetzman
authors.forename: Lisa G
authors.initials: LG
authors.lastname: England
authors.forename: Cindy M
authors.initials: CM
authors.lastname: Cave
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Seitz
authors.forename: Cristina N
authors.initials: CN
authors.lastname: Mazuski
authors.forename: Tony T
authors.initials: TT
authors.lastname: Zhou
authors.forename: Michel
authors.initials: M
authors.lastname: Morre
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hotchkiss
authors.forename: David A
authors.initials: DA
authors.lastname: Hildeman
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D020381:Interleukin-17 / Q000096:biosynthesis*; D015851:Interleukin-7 / Q000008:administration & dosage / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000401:mortality / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D020381:Interleukin-17; D015851:Interleukin-7; D016692:Receptors, Antigen, T-Cell, gamma-delta
references.citation: Intensive Care Med. 2004 Mar;30(3):408-15
references.pmid: 14722631
references.citation: PLoS One. 2007 Sep 05;2(9):e853
references.pmid: 17786224
references.citation: Shock. 2005 Jul;24(1):40-7
references.pmid: 15988319
references.citation: Blood. 2001 Feb 1;97(3):601-7
references.pmid: 11157474
references.citation: BMC Immunol. 2010 Jan 25;11:4
references.pmid: 20100328
references.citation: J Leukoc Biol. 2005 Aug;78(2):325-37
references.pmid: 15817707
references.citation: Nature. 1995 Jan 19;373(6511):255-7
references.pmid: 7816142
references.citation: Immunity. 2009 Aug 21;31(2):321-30
references.pmid: 19682928
references.citation: Shock. 2008 May;29(5):591-7
references.pmid: 17885647
references.citation: Shock. 2007 Nov;28(5):576-81
references.pmid: 18084824
references.citation: Nat Rev Immunol. 2003 Mar;3(3):233-42
references.pmid: 12658271
references.citation: J Immunol. 2010 Apr 1;184(7):3768-79
references.pmid: 20200277
references.citation: Shock. 2007 Sep;28(3):334-8
references.pmid: 17545945
references.citation: Infect Immun. 2009 Jan;77(1):485-91
references.pmid: 19001080
references.citation: J Immunol. 1994 May 15;152(10):5014-21
references.pmid: 8176219
references.citation: Crit Care Med. 2001 Jul;29(7):1303-10
references.pmid: 11445675
references.citation: Blood. 2008 Jan 1;111(1):42-9
references.pmid: 17928531
references.citation: J Exp Med. 2008 Jul 7;205(7):1701-14
references.pmid: 18573906
references.citation: J Immunol. 2001 Jun 1;166(11):6952-63
references.pmid: 11359857
references.citation: Cytokine Growth Factor Rev. 1998 Jun;9(2):167-73
references.pmid: 9754710
references.citation: Shock. 2007 May;27(5):507-19
references.pmid: 17438456
references.citation: Inflamm Res. 2010 Oct;59(10):809-16
references.pmid: 20372968
references.citation: Shock. 2003 Aug;20(2):123-9
references.pmid: 12865655
references.citation: Immunity. 2009 Aug 21;31(2):331-41
references.pmid: 19682929
references.citation: Lancet. 2004 May 22;363(9422):1721-3
references.pmid: 15158636
references.citation: Shock. 2010 Oct;34(4):377-83
references.pmid: 20610943
references.citation: Annu Rev Immunol. 2007;25:821-52
references.pmid: 17201677
references.citation: Nat Rev Immunol. 2009 Aug;9(8):556-67
references.pmid: 19575028
references.citation: J Immunol. 1999 Aug 1;163(3):1537-44
references.pmid: 10415057
references.citation: Crit Care Med. 1999 Jul;27(7):1230-51
references.pmid: 10446814
references.citation: Shock. 1999 Aug;12(2):118-26
references.pmid: 10446892
references.citation: J Virol. 2009 Sep;83(17):8604-15
references.pmid: 19515766
references.citation: J Immunol. 2009 Jun 15;182(12):7846-54
references.pmid: 19494309
references.citation: Am J Physiol Regul Integr Comp Physiol. 2006 Nov;291(5):R1338-43
references.pmid: 16793935
references.citation: J Immunother. 2006 May-Jun;29(3):313-9
references.pmid: 16699374
references.citation: J Immunol. 2005 Apr 15;174(8):5110-8
references.pmid: 15814742
references.citation: J Immunol. 2001 Dec 1;167(11):6140-9
references.pmid: 11714773
references.citation: Shock. 2002 Dec;18(6):487-94
references.pmid: 12462554
references.citation: Eur J Immunol. 1997 Jul;27(7):1704-12
references.pmid: 9247581
references.citation: Shock. 2002 Jun;17(6):463-7
references.pmid: 12069181
references.citation: Annu Rev Immunol. 2007;25:193-219
references.pmid: 17129180
references.citation: Immunology. 2003 Mar;108(3):365-74
references.pmid: 12603603
references.citation: Biochem Biophys Res Commun. 2007 Sep 21;361(2):533-6
references.pmid: 17662241
references.citation: Curr Opin Immunol. 2008 Jun;20(3):353-7
references.pmid: 18439808
references.citation: Blood. 1998 Dec 15;92(12):4742-9
references.pmid: 9845540
references.citation: J Immunol. 1999 Apr 1;162(7):4148-56
references.pmid: 10201940
references.citation: Methods Enzymol. 1986;132:198-204
references.pmid: 3102897
references.citation: Blood. 1997 Aug 1;90(3):909-28
references.pmid: 9242519
references.citation: FASEB J. 2008 Jul;22(7):2198-205
references.pmid: 18299333
references.citation: J Virol. 2008 Oct;82(19):9564-76
references.pmid: 18667515
references.citation: J Immunol. 2000 Jun 15;164(12):6322-31
references.pmid: 10843686
references.citation: J Exp Med. 2001 Aug 20;194(4):519-27
references.pmid: 11514607
references.citation: J Leukoc Biol. 2004 Mar;75(3):443-52
references.pmid: 14673016
references.citation: Adv Immunol. 2005;87:27-59
references.pmid: 16102571
references.citation: Blood. 2001 Dec 1;98(12):3309-14
references.pmid: 11719368
references.citation: Shock. 2010 Oct;34(4):327-36
references.pmid: 20386500
references.citation: Nat Rev Immunol. 2006 Nov;6(11):813-22
references.pmid: 17039247
references.citation: J Exp Med. 1996 Jun 1;183(6):2593-603
references.pmid: 8676080
references.citation: Shock. 2010 Oct;34(4):358-63
references.pmid: 20220566
references.citation: Mol Med. 2008 Jan-Feb;14(1-2):64-78
references.pmid: 18026569
references.citation: J Immunol. 2002 Apr 1;168(7):3195-204
references.pmid: 11907072
references.citation: J Leukoc Biol. 2008 Mar;83(3):581-8
references.pmid: 18063696