Canicul innundogy (goou) 427 , 30s-152 Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: Implications for Th17-mediated inflammation in auto-immunity Chun Kwok Wong a,1, Lydia Choi Wan Lit a,,1, Lai Shan Tam b, Chun Kwok Wong Edmund Kwok Ming Li "Bepartment of Chersical Aatholew The Chicese Univendey of Hone Kone, Arince of Walen haspitaf, Shatio, hone Ksong Fapa, Macau Aeceteed 19 suly 200?; accepted with revision 17 Janumry aocs dealable astine 25 Mirch 2008 Mbutract 1.-23-dependent. IL-17-producing T helper (T) bimphocyten are ansciated weth flaw cptonstry. Plannu IL-12, IL.17, 1.21 and CXCL 10 concentration and the number of Th17 cella were xignificantly welerwabed in 2 E patients than contsal a ubjects (bathp-a.as). Elovabed L12, 1-1T and CicLod concentrationa carrelated poetthely and signticanthy wath yeDa fall p-a.05). Flasu L-12 and L-1T ahowed aignificant and posthe cormblucion with plasu The chenolde CecL 10 concmination in sue pacionta (all pea.0s). Ex vire inductions of L-1J by (all p.0.00p. The activated L-21/L. 17 ash is inportate for the inflaminatary inmuntify in 21E. o 2 Dos elevier linc. All rights reourned. lntroduction T and 8 hymptocyten and aubiequent polyclonal actieation of circulating 8 bymphecytes that produces a large quatity Syaternic lupes erpthamateun (5LE) in a pratotypic vaternic of autareuctive artibodies [1]. it has been aureated that However, ether atualin hire dernasstrated that the Hong Kang Fax +1522632900 . immune respanes huve been gererally comidered to be C-nal addeus waskellumicutk edutk (C. W.K. Lamp. putholsical in autsinume dhease via the induction of inflammatery reaction [5]. 1321-Le16/5 - iee front rutber 6 ance thevier inc. Nill righta nearved.IL- 2.317 iw in SLE 387 Results and creatirine concentration, and druz treatment are urnmirhed in fable 1. Unitg a SLEDN citaff vcawa 6 , the SLE patients and ceetrol subjects praportians of the SLE graup and ISLE arap with active age-matched control sebjects piC group) werestudied. Their pyuria. The mein glamerulasephritis duration af isLL age, ses, deracian af dagninh, siephl icere, plasina urea putients was 6.6 yeirz. Plasma cytokines and chemokint Table 1 Characteritici of MSE and SE patinita and control Tubjuct. Phavna L-12, 1L-17, 1L-23 and CXCL10 cancentratiom were vigntica-tly higher in all SLE patiets as mel an lisLE and 2.E eroups thin in cortrol sebjocti (Table 2). Mil SLE patients huve devated plinma L-17 concertiration compared with centrol mbjocti. L-17 and Ciols thowed the freatentpind.06, data not thawniCirculating IL-17a secreting Titi cels Correlations between plasma IL-12, L-17 and Aashew in fie. 1, the number of circalating IL- 17i secesing CoLio Thil celh in 9 if patienta man vignica-tly higher than that PMA and ianernycin mere commorhy uned atinulators to carrelatiom of plinima IL-12 and IL-17 concertratiorn with actovate the expremion of IL-17 in Th1J cels accerding to CoCL.10 in FiF and SLE patienta.

1. Canicul innundogy (goou) 427 , 30s-152 Hyperproduction of IL-23 and IL-17 in patients with
systemic lupus erythematosus: Implications for Th17-mediated inflammation in auto-immunity
Chun Kwok Wong a,1, Lydia Choi Wan Lit a,,1, Lai Shan Tam b, Chun Kwok Wong Edmund Kwok
Ming Li "Bepartment of Chersical Aatholew The Chicese Univendey of Hone Kone, Arince of
Walen haspitaf, Shatio, hone Ksong Fapa, Macau Aeceteed 19 suly 200?; accepted with revision
17 Janumry aocs dealable astine 25 Mirch 2008 Mbutract 1.-23-dependent. IL-17-producing T
helper (T) bimphocyten are ansciated weth flaw cptonstry. Plannu IL-12, IL.17, 1.21 and CXCL 10
concentration and the number of Th17 cella were xignificantly welerwabed in 2 E patients than
contsal a ubjects (bathp-a.as). Elovabed L12, 1-1T and CicLod concentrationa carrelated
poetthely and signticanthy wath yeDa fall p-a.05). Flasu L-12 and L-1T ahowed aignificant and
posthe cormblucion with plasu The chenolde CecL 10 concmination in sue pacionta (all pea.0s).
Ex vire inductions of L-1J by (all p.0.00p. The activated L-21/L. 17 ash is inportate for the
inflaminatary inmuntify in 21E. o 2 Dos elevier linc. All rights reourned. lntroduction T and 8
hymptocyten and aubiequent polyclonal actieation of circulating 8 bymphecytes that produces a
large quatity Syaternic lupes erpthamateun (5LE) in a pratotypic vaternic of autareuctive artibodies
[1]. it has been aureated that However, ether atualin hire dernasstrated that the Hong Kang Fax
+1522632900 . immune respanes huve been gererally comidered to be C-nal addeus
waskellumicutk edutk (C. W.K. Lamp. putholsical in autsinume dhease via the induction of
inflammatery reaction [5]. 1321-Le16/5 - iee front rutber 6 ance thevier inc. Nill righta nearved.IL-
2.317 iw in SLE 387 Results and creatirine concentration, and druz treatment are urnmirhed in
fable 1. Unitg a SLEDN citaff vcawa 6 , the SLE patients and ceetrol subjects praportians of the
SLE graup and ISLE arap with active age-matched control sebjects piC group) werestudied. Their
pyuria. The mein glamerulasephritis duration af isLL age, ses, deracian af dagninh, siephl icere,
plasina urea putients was 6.6 yeirz. Plasma cytokines and chemokint Table 1 Characteritici of
MSE and SE patinita and control Tubjuct. Phavna L-12, 1L-17, 1L-23 and CXCL10 cancentratiom
were vigntica-tly higher in all SLE patiets as mel an lisLE and 2.E eroups thin in cortrol sebjocti
(Table 2). Mil SLE patients huve devated plinma L-17 concertiration compared with centrol
mbjocti. L-17 and Ciols thowed the freatentpind.06, data not thawniCirculating IL-17a secreting Titi
cels Correlations between plasma IL-12, L-17 and Aashew in fie. 1, the number of circalating IL-
17i secesing CoLio Thil celh in 9 if patienta man vignica-tly higher than that PMA and ianernycin
mere commorhy uned atinulators to carrelatiom of plinima IL-12 and IL-17 concertratiorn with
actovate the expremion of IL-17 in Th1J cels accerding to CoCL.10 in FiF and SLE patienta 0.12 r
=0.484,p=0.005; previas itudy (2.7). Na 1L.17A secreting Tht 7 celh mas r=6.383,p=0.069;1217:r=
0.331,p=0.037;r=6.123; ierimyciecdati ret ahowel. carrelation of plavma lL-2s with cxti.10 in all
greupn of SLe Correlatien between dieate actheity and plama patienta call pe 0.0.5, daba nat
ihawni. cytowines and chamoline Ex wivo preduction of IL-12, L-17 and IL-23 Ai shoen in Fig. 2,
there were signticant ard ponitive We firitly ievestigated the ex novo production of iL-17 inom mith
SLED acori. While the plinma level of L-17 ahowed a actielion in the patiant cohart. IL-23 could
aigetfica-tly eroupt (foL.: r=0.363,p=0.021 and SLE: r=0.336,p=0.004, imventigated the ex vivo
productian of L-12, L-17 and IL.2.3 (B) () without renal dhease jn=40p. Spearimaris rark correlation
teat wan ined to mues the corselationa of plaurna concentrations of crtskinen and chemskene
wten yieDW score.Irom arti-CD] and inti-CDas co-atimulated PEuC upon pre. ret shaw ary

2. correlation with the daagen ef predrisalase, could aignificantiy induce the es vivo releine of IL-17
and IL. (fromotien of f cell exparaion and probileration) and signiticantiy higher in all SLE patients
than that in NC eroup esprevian and the differentiatian of the ind The 7 celh in ieverth Similirly,
there was an inductian in the ex vive releine of scriptian facter Cata-3 and The cytsite il-4 in SLL
patienti, ever, we ebnerved na ajgetficant elfference in the L-12 increine in plasma concentratiam
of L-12 farrily cyebkines productienbetween the putiont and coetral eroupa whin the L-12 and L-2.,
and IL-17 with Th1 chemekine CxtL.10 data nat ahownifarrily medated Th1 and aule-ieflarmatary
procesies of 4. as esemplifind by therr petitive correlatisen with disene Dixcusion activity The
expresian of Citlio fram a viriaty af celh,were aigniticintly higher in actiee 9.2 patienti (5LED : 16)
than these in the inketive SLE pueienta plEDWI 10 j [33]. Arether study of hat et al. reperted the
decreaie in the ex vive prodection of IL-12 fram BEuC atimalated by LPS and IFW-Y [34]. On the
other hand, folans et al and our previoun study hive shem an elevation of serum lL-12 in 3.1
patienti. and high concestration of 112 were alsa avociated with increased lerel of Th1 cpaskine P
F4-y but decreined level of Thl cyeskine [L-13 [4,21). heur prenent atedy, eur findings of elareated
L-12 and its pontive carreleian with SLEDO min. abe in concordance with the previoun reperti.
However, Tigure 5 Ex vive prodection at IL. 17 and IL-Is from anti-cod, arti-coas and L-18
activated paMC of gE and NC group in=21 and 11 far L.1T and IL.23, reipecthelyj. The culture
apernutant wan dertied from paMc cultured with medium wth or without anti-CDs aritbody, anti-
Coas artibody (1 adyinL each) and IL- II (20 ne /mL) far 24h. Arulth are prenented wth Eos.
aponding treutment grouph. cod: ants-cod artibody, coel: antscode antibedy Me: no rignticance.