%PDF-1.7 % 450 0 obj <>stream hތ̱ 0WIZR _ MR H/ě7_ 6z`K_scIkm>jϫ62@o rkk*iz 098 endstream endobj 451 0 obj <>stream h214P0P014T06Ww/+Q0L) (T$a*2( H,J M B`  endstream endobj 452 0 obj <>stream hޜVMs0+{CK10SIKp0BŸVR liN;`gxd@3%x HOy8e "x%E1N2 )Q3%~@1,4 4T DMSL(PB7 (0ʀy _/8kZ绪R8_C=loצkI#;׿7eHDZxkV_փ/5֕7MV7eSBϲ7zy(z0Q 8c꛿= uenF,e//gm{6/O*/4dz2±ݖ#bj`ŢV%<)YpU%jŘWn+ E滱qge1[5n}KS~^Oן*AϏ?mCr]z (Aa1[O{b"vzUL;(U8,xvWm+[S=ϲxs'J1@$r5ވew1Z{]xUV/+X5;S|Z:MJ]:>nQ۬ϧ癥VcSay';N wu0QB?e&F6-YBc̯WPDq endstream endobj 453 0 obj <>stream hĖmo0?_$ReHm76&EF%V$@_u*;gs #J2"JND3$ #\(p)O%(!SD0L‰E $^핷&Hr5(dua]EӁqn5.yIJ;<>stream hޜUMs6eO=?-2oxƱԱj,M(H$mǷ}%[;LoE xu#E]m;];{4c`vݐ1 G=#:>u8eK;ל{Ϸkj*V|]pfu{k JyG»v ,aQ>4Y8VqU -8sfϱq}OTYd8 O+_eLNMƹuٲXT"$JsUsQ&@dq]ɯ%ۓs gsvk9EuZoJ><]L/(B 噦ko1t|d $Fސڝ}Qޏ=܂n~ZL~? f L Cp SW Tp~3Qp[mnN1&&{  -~90n<XW #* %&>stream hd0D-6 DO&z#Ժ1\(iy{;r!EQ@'‰ʿ*W+_;WЃ v 8ό,ႏŴJB+VuFN>T$Ob?سKUmGmN`MW>v,SXmő}bY~N} endstream endobj 456 0 obj <>stream h211S0P011U03PwJ,Nu+яJ,HsKOJ,)KM$&T C0Rng#5,$39Q5/9?h K=A@M0]0[ endstream endobj 110 0 obj <>stream GPL Ghostscript 9.50 type 1 diabetes; type 3 innate lymphoid cells; regulatory T cells; interleukin-2; gut-associated lymphoid tissue; lamina propria 2023-04-17T00:55:46+02:00 2023-04-17T00:55:46+02:00 LaTeX with hyperref uuid:5f7a5fd9-14c6-11f9-0000-74e9d13f496c uuid:5f7a5fd9-14c6-11f9-0000-74e9d13f496c application/pdf Tamara Saksida, Verica Paunović, Ivan Koprivica, Dragica Mićanović, Bojan Jevtić, Natalija Jonić, Ivana Stojanović and Nada Pejnović Recent data indicate the link between the number and function of T regulatory cells (Treg) in the gut immune tissue and initiation and development of autoimmunity associated with type 1 diabetes (T1D). Since type 3 innate lymphoid cells (ILC3) in the small intestine are essential for maintaining FoxP3+ Treg and there are no data about the possible role of ILC3 in T1D pathogenesis, the aim of this study was to explore ILC3-Treg link during the development of T1D. Mature diabetic NOD mice had lower frequencies of IL-2-producing ILC3 and Treg in small intestine lamina propria (SILP) compared to prediabetic NOD mice. Similarly, in multiple low doses of streptozotocin (MLDS)-induced T1D in C57BL/6 mice, hyperglycemic mice exhibited lower numbers of ILC3, IL-2+ ILC3 and Treg in SILP compared to healthy controls. To boost T1D severity, mice were treated with broad-spectrum antibiotics (ABX) for 14 days prior to T1D induction by MLDS. The higher incidence of T1D in ABX-treated mice was associated with significantly lower frequencies of IL-2+ ILC3 and FoxP3+ Treg in SILP compared with mice without ABX treatment. The obtained findings show that the lower proportions of IL-2-expressing ILC3 and FoxP3+ Treg in SILP coincided with diabetes progression and severity. endstream endobj 112 0 obj <>stream 2023-08-29T09:07:26+01:00 2023-08-29T09:00:12+01:00 2023-08-29T09:07:26+01:00 Adobe Acrobat Pro 2020 20.5.30514 application/pdf Microsoft account uuid:0ca3b005-6cf3-4c75-94a2-dac9db9c13c5 uuid:3fff7d38-2f92-4d3d-adb9-3f6f802df58d Adobe Acrobat Pro 2020 20.5.30514 endstream endobj 415 0 obj <>/Metadata 112 0 R/Outlines 372 0 R/Pages 410 0 R/StructTreeRoot 396 0 R/Type/Catalog>> endobj 426 0 obj <>stream x `ՙ?itH#辭d\$;E!$>$#Rl[vY]ғ# Pz@۲m{Or8H#yǼyKi9]n,\ap5/\Kw'p4oo6Ik;6Uo^Kvwu~Kh`_sI׵Z/h[n8k3b?pV M/ٝ AebZږ&7lmM/ >`8~7\tǞh6tebذ 4?iP7.J @5XX|M[‡qW_sХwX&_t`Eoip$6_|.\^4ۦq<ߋ7  /lKxKI͗mρn @7F9ZB?#go"WbV 85Foexw_dkF2d8MGpZA+e<=z]j ^rPWKGt/kS/];4S͏IR䙂0K$-8-ATGu8]8vp:ŘT iSƴ&1}Vm@֟QLq>;U𵔮r!(UCKvQ2ec8bތn8y,ܭHwqځc]ӥ8?ݢy1΋qeǸ띘גn N-YAapB;A >7=5p^s>6&xF_ٷJqkfr"u}`0 Ԣ7@ǐ+3V(&H=c&`0 `0 `0 c֫` =tAb`0VU[rC#r0\3Žm>3?*'Ae鵱Pӽʩ[1=8{ܺ7;:;ޫܴ6궰9Ա"ͷ0氪?2޳0u"wdϿǻ= k֬N_=P>cΩF~CM֬ďѼ|ǘh>є{ `9FO&8єWM&Q2ׅua,qj*5S4Zh.~ TQ}9NE 0)OPMT`N DQ-T`AP$TU;Ȩw 6TQD/xjB!%@ CUA D 0j R?C"eE-ZJVAj5@EJ:Bթ?+נ6B-TӠ>G 3΄)MИoSQa:l-0u\:PЌ:mh٨mЂ栶:`BHvR]SobhE]mKa2hO g@rXJL`1jnXz&,Mg2Գr^XzLR] Pσ.5Н:kL>8 F@}u:碮G}6jԍpT/BCQ7QR/%0֡~P/pl@Br؈zQ0uz\1؄q8"\M،z-|:`+\z=\ ؂Izܐ܈EӸԗ&W3_Q`/p+]Ym߀ϡ+|nP;P _D9w˨߆;;T _ŒPO5 :. u}CWQ w?S |u|33?D}~#ԇP}K=ᇨPO$<^1Sx8 gaWI?EO99o'TD= yx(8Q#//cpax %xe*A={Q_: Q #}%l?='N8B`{|<ɨOx^0A(F7o2P<O21%0$]F x#/Zc^u- Pœ(Aݭ2LFz#r HN9SB`DIis'鎉'IF^-xڠѠCg$$##9Ao+`c{IFՓHƓ0*<0x=`0THl3Qb=$evxhƝ&ޠyO1gc2wiNd)QsxPkg0EF*i u:cxd2 <`1f) mK"휑3yO¹6f'9ƓM #GRI`0 /,W~*""9(o4NM=o$|N1Uz v\5$j $Ag,x,$$ VQD RX#9?IsfD' J?6ta$FO* ZY) P!iIq7#7eSLj,yxQbHǶml,`٬6Yʲ'{*Yo `'vbCg,vJϜ7B>3-;GI$l.h|qJp `0*N[jNN{D';E^$SL8Ej6YqbVED谈9{D vܨx vQd3\h$A(ykv&79d!9p2 ZE^IL앬"l [6"If,y$C'"z vj<)T3"$|htl;oB{2z$qcAqnOȓ*$I  38cN ^Pr gēl'dCIL4ԼǘqBԍbҡS`0*M[jx҇,Y%,K,}#L#la8.9v&]΋WmO*QsAP vQd"IOe'yn^ yvxxDI$d|$e6>O"vZIc*'M>'[ Hk`0 G%4Qu#s$;6b 'vdu8]v9X.ߦ~D9œL*@Pkg0E&8`NGhD\Y09 x0K~w$p|NO ^+!`BfK69!۩%$I$WigL y11vv+C_\!0 jn6sa v wN9;vv&]&e\6jw9BNGNū6R}쨹Yj TuG ^,vI X@*%%*)/p]v-]bt$Yt9C.G^wQ*-eB3QkAM;#f*PGC ٭}Uw`0 >喚>ʧ=i:˳9%J:>Gܸݲӵ]\Uz<^F PU3"SmHEIxtR`e$⏄!EΞ8Eu=nn;;Ġ6xR:$U=~+qyN6b7ș|qJp0ԭ. 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