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首页 > 生物资讯 > 产品通讯 > 肿瘤坏死因子TNF配体及受体超家族成员

肿瘤坏死因子TNF配体及受体超家族成员

作者:池博专刊    发布日期:2021-03-23 09:00


首次注意到肿瘤坏死因子TNF的存在,是因为观察到癌症患者在细菌感染后偶尔表现出肿瘤的自发消退。后续1960年代的研究表明,响应细菌产物而产生的宿主相关(或内源性)介体可能与观察到的效应有关。1975年,发现一种细菌诱导的循环因子对植入小鼠皮肤的肿瘤具有很强的抗肿瘤活性,称其为肿瘤坏死因子(TNF),随后该基因被分离,克隆,成为一个与免疫调节和炎症有关的分子家族的原型。

 

—  联 科 生 物 — 

自主研发ELSIA试剂盒10年,向国际顶尖ELISA试剂盒看齐,质控严格,价格便宜。目前已开发的TNF超家族成员ELISA试剂盒如下,新品不断。欢迎垂询!
 

系统名称
目录号
产品名称
TNFSF1
70-EK1139
Human TNF-β/Lymphotoxin-α ELISA Kit
TNFSF2
70-EK182
Human TNF-a ELISA Kit
TNFSF2
70-EK182HS
Human TNF-α High Sensitivity ELISA Kit
TNFSF6
70-EK1F02
Human Fas Ligand/TNFSF6 ELISA Kit
TNFSF10
70-EK1161
Human TRAIL/TNFSF10 ELISA Kit
TNFSF11
70-EK1208
Human TRANCE/TNFSF11/RANKL ELISA Kit
TNFSF12
70-EK1256
Human TWEAK ELISA Kit
TNFSF13B
70-EK1102
Human BAFF/BlyS/TNFSF13B ELISA Kit
TNFSF14
70-EK1217
Human CD258/LIGHT/TNFSF14 ELISA Kit
TNFSF15
70-EK1268
Human TL-1A/TNFSF15 ELISA Kit
TNFRSF1A
70-EK1109
Human sTNF RI/TNFRSF1A ELISA Kit
TNFRSF1B
70-EK1123
Human sTNF RII/TNFRSF1B ELISA Kit
TNFRSF6
70-EK1F01
Human Fas/TNFRSF6/CD95 ELISA Kit
TNFRSF8
70-EK1311
Human CD30/TNFRSF8 ELISA Kit
TNFRSF9
70-EK1263
Human 4-1BB/TNFRSF9/CD137 ELISA Kit
TNFSF2
70-EK282/3
Mouse TNF-a ELISA Kit
TNFSF2
70-EK282HS
Mouse TNF-α High Sensitivity ELISA Kit
TNFSF10
70-EK2161
Mouse TRAIL/TNFSF10 ELISA Kit
TNFSF11
70-EK2208
Mouse TRANCE/TNFSF11/RANKL ELISA Kit
TNFSF13B
70-EK2102
Mouse BAFF/BLyS/TNFSF13B ELISA Kit
TNFRSF6
70-EK2F01
Mouse Fas/TNFRSF6/CD95 ELISA Kit
TNFRSF8
70-EK2311
Mouse CD30/TNFRSF8 ELISA Kit
TNFSF2
70-EK382/3
Rat TNF-a ELISA Kit
TNFSF2
70-EK382HS
Rat TNF-α High Sensitivity ELISA Kit
 
70-EK1157
Human Pentraxin 3/TSG-14 ELISA Kit
 


一、 人类和小鼠中TNF配体/受体超家族成员


在哺乳动物中,TNF配体超家族(TNFSF)通过TNF受体超家族(TNFRSF)的成员发出信号,激活在发育、器官发生、细胞死亡和存活中起生物学作用的信号通路。最早发现的TNFSF成员是TNF和淋巴毒素α(Ltα)。随着人类和小鼠基因组大规模测序的完成,几乎所有的TNFSF和TNFRSF成员现在都被鉴定出来。在人类(表1)和小鼠(表2)中都有19个TNF配体。需要注意,一些序号例如TNFSF16/17是没有对应基因的,我们没有追溯原因。另外,TNFSF12-TNFSF13是由TNFSF12的细胞质和跨膜结构域与TNFSF13的C端结构域融合而成的杂交蛋白。该杂交蛋白膜锚定并在细胞表面呈现TNFSF13的受体结合域。 TNFSF配体是具有细胞内N端和细胞外C端结构域的Ⅱ型膜结合蛋白。在人类和小鼠中描述的19种已知配体中,有11种编码蛋白水解裂解位点,产生具有生物活性的可溶性形式。在C末端,它们包含TNF同源结构域(THD)。配体成员之间的保守性较弱(20–30%),THD结构能够将每个TNF配体组装成锥形三聚体。
 

表1. 人类中TNF配体超家族成员

 

Name Location Aliases MIM*
TNFSF1 Chromosome 6, NC_000006.12
(31560550..31574324)
TNFSF1B, TNFB, LTA, LT, TNLG1E 153440
TNFSF2 Chromosome 6, NC_000006.12
(31575565..31578336)
TNFSF1A, TNFA, DIF-alpha,
TNLG1F, TNF
191160
TNFSF3 Chromosome 6, NC_000006.12
(31580558..31582425, complement)
LTB, TNFC, TNFSF3, TNLG1C, p33 600978
TNFSF4 Chromosome 1, NC_000001.11
(173183729..173462208, complement)
CD134L, CD252, GP34,
OX-40L, OX4OL, TNLG2B, TXGP1
603594
TNFSF5 Chromosome X, NC_000023.11
(136648158..136660390)
CD154, CD40L, CD40LG, HIGM1,
IGM, IMD3, T-BAM, TNFSF5,
TRAP, gp39, hCD40L
300386
TNFSF6 Chromosome 1, NC_000001.11
(172659103..172666876)
ALPS1B, APT1LG1, APTL,
CD178, CD95-L, CD95L, FASL,
FASLG, TNFSF6, TNLG1A
134638
TNFSF7 Chromosome 19, NC_000019.10
(6581648..6591150, complement)
CD27-L, CD27L, CD27LG,
CD70, LPFS3, TNFSF7, TNLG8A
602840
TNFSF8 Chromosome 9, NC_000009.12
(114893343..114930674, complement)
CD153, CD30L, CD30LG, TNLG3A 603875
TNFSF9 Chromosome 19, NC_000019.10
(6531026..6535924)
4-1BB-L,
CD137L,
TNLG5A
606182
TNFSF10 Chromosome 3, NC_000003.12
(172505508..172523430, complement)
APO2L, Apo-2L, CD253,
TL2, TNLG6A, TRAIL
603598
TNFSF11 Chromosome 13, NC_000013.11
(42562736..42608013)
CD254, ODF, OPGL, OPTB2, RANKL,
TNLG6B, TRANCE, hRANKL2, sOdf
602642
TNFSF12 Chromosome 17, NC_000017.11
(7549058..7557881)
APO3L, DR3LG, TNLG4A, TWEAK 602695
TNFSF12-
TNFSF13
Chromosome 17, NC_000017.11
(7549058..7561601)
TWE-PRIL  
TNFSF13 Chromosome 17, NC_000017.11
(7558282..7561601)
APRIL, CD256, TALL-2,
TALL2,TNLG7B,TRDL-1,
UNQ383/PRO715, ZTNF2
604472
TNFSF13B Chromosome 13, NC_000013.11
(108268240..108308484)
BAFF, BLYS, CD257, DTL,
TALL-1, TALL1,THANK,
TNFSF20, TNLG7A, ZTNF4
603969
TNFSF14 Chromosome 19, NC_000019.10
(6658126..6670595, complement)
CD258, HVEML, LIGHT, LTg 604520
TNFSF15 Chromosome 9, NC_000009.12
(114784635..114806039, complement)
TL1, TL1A, TNLG1B,
VEGI, VEGI192A
604052
TNFSF18 Chromosome 1, NC_000001.11
(173039202..173050941, complement)
AITRL, GITRL, TL6,
TNLG2A, hGITRL
603898
EDA Chromosome X, NC_000023.11
(69616086..70039472)
ECTD1, ED1, ED1-A1,
ED1-A2-A1,EDA-A2,EDA1,
EDA2, HED, HED1,
ODT1, STHAGX1,TNLG7C,
XHED, XLHED, EDA
300451

在线人类孟德尔遗传数据库OMIM(https://omim.org/entry/)中该基因编号。
 

表2. 小鼠中的TNF配体超家族成员
 

Name Location Aliases
TNFSF1 Chromosome 17, NC_000083.7
(35422141..35424568, complement)
Tnfsf1b, Lta, L, LT, LT-, LT-[, LT-[a],
LT-alpha, LT[, LT[a], LTalpha, Ltx,
TNF-be,TNF-beta, TNFSF1, Tnf, Tnfb,
Tnfsf,Tnlg1e, hlb38, hlb382, lymph
TNFSF2 Chromosome 17, NC_000083.7
(35418343..35420983, complement)
Tnfsf1a, DI, DIF, TNF-,
TNF-a,TNF-alpha, TNFalpha,
Tna,Tnfs, Tnlg1f, Tnf
TNFSF3 Chromosome 17, NC_000083.7
(35413483..35415281)
Ltb, AI662801, LTbe,
LTbeta,Tnf, Tnfc, Tnfs,
Tnfsf3,Tnlg1c, p3, p33
TNFSF4 Chromosome 1, NC_000067.7
(161223009..161245777)
Ath, Ath-, Ath-1, Ath1,
CD134, CD134L, OX-40L, OX4,
Ox40l, TXGP1, Tnlg2b, Txgp,
Txgp1l, gp3, gp34
TNFSF5 Chromosome X, NC_000086.8
(56257503..56269402)
CD154, CD40-L, Cd40, Cd40l,
Cd40lg, HIGM, HIGM1, IGM,
IMD, IMD3, Ly-6, Ly-62, Ly62,
T-BA,T-BAM, TRAP, Tnfs,
Tnfsf5,Tnlg8b, gp3, gp39
TNFSF6 Chromosome 1, NC_000067.7
(161608260..161616064, complement)
APT1, APT1LG1, CD178,
CD95,CD95-L, CD95L, F,
Fa,Fas-Lg, Tnfs, Tnfsf6,
Tnlg1a,gld, Fasl
TNFSF7 Chromosome 17, NC_000083.7
(57452997..57456777, complement)
CD27LG, Cd27l, Tnfs,
CD70, Tnfsf7, Tnlg8a
TNFSF8 Chromosome 4, NC_000070.7
(63749439..63779745, complement)
CD153, CD30LG,
Cd30, Cd30l, Tnlg3a
TNFSF9 Chromosome 17, NC_000083.7
(57412113..57414757)
4-1BB, 4-1BB-, 4-1BB-L, 4-1BBL,
AI848817, Cd137, Cd137l, Ly6, Ly63l
TNFSF10 Chromosome 3, NC_000069.7
(27371226..27393814)
A330042I21Rik, AI448571, AP,
APO-2L, Ly81, T, TL2, Tnlg6a, Trail
TNFSF11 Chromosome 14, NC_000080.7
(78514886..78545483, complement)
Ly10, Ly109l, O, OD,
ODF, OPGL,R, RANKL,
Tra, Trance
TNFSF12 Chromosome 11, NC_000077.7
(69577066..69586924, complement)
A, Apo3l, DR, Dr3l,
Dr3lg, Twea, Tweak
TNFSFm13 Chromosome 11, NC_000077.7
(69573403..69586924, complement)
Tnfsf12-Tnfsf13, TWE-,
Tnfsf12Tnfsf13, Tnfsf12tnfsf13,
Twe-pril
TNFSF13 Chromosome 11, NC_000077.7
(69573403..69576380, complement)
2310026N09Rik, April, TA,
TRD, Tall2, Tnlg7b, Trdl1
TNFSF13b Chromosome 8, NC_000074.7
(10056229..10086000)
BAF, BAFF, BL, BLyS,
D8Ertd387, D8Ertd387e,
TAL, TALL-1, TALL1,
THANK, TNFSF20,
Tnlg7a, zTNF, zTNF4
TNFSF14 Chromosome 17, NC_000083.7
(57496474..57501181, complement)
HVEM, HVEM-L, HVEML,
LIG, LIGHT, LTg,
Ly113, Tnlg1d
TNFSF15 Chromosome 4, NC_000070.7
(63642837..63663296, complement)
TL, Tl1, Tl1a,
Tnlg1b, VE, Vegi
TNFSF18 Chromosome 1, NC_000067.7
(161322226..161332859)
Gi, Gitrl, Tnlg2a
Eda Chromosome X, NC_000086.8
(99019212..99444366)
EDA1, Ed1-, Eda-A1,
Eda-A2, HED, Ta, Tnlg7c,
XLHED, tabby, Eda


迄今为止,在哺乳动物中已鉴定出29种TNF受体,这些受体的主要特征是有一个富含半胱氨酸的结构域(CRD),由围绕CXXCXXC核心基序的三个二硫键组成,形成一个拉长的分子。家族成员中CRD的数量从BAFFR(TNFRSF13C)或BCMA(TNFRSF17)只包含一个CRD到CD30(TNFRSF8)包含六个CRD。这些受体多数是Ⅰ型膜蛋白,其中BAFFR(TNFRSF13C)、BCMA(TNFRSF17)、TACI(TNFRSF13B)和XEDAR(TNFRSF27)是Ⅲ型膜蛋白,OPG(TNFRSF11B)和DcR3(TNFRSF6B)是分泌型的。一般来说,一个三聚体配体与三个单体受体结合。人类中所有TNF家族受体成员列于表3,小鼠的列于表4。

 

表3. 人类中TNF家族受体成员
 

Name Location Aliases MIM
TNFRSF1A Chromosome 12, NC_000012.12
(6328771..6342076, complement)
CD120a, FPF, TBP1, TNF-R,
TNF-R-I, TNF-R55, TNFAR,
TNFR1, TNFR55, TNFR60,
p55, p55-R, p60
191190
TNFRSF1B Chromosome 1, NC_000001.11
(12166948..12209222)
CD120b, TBPII, TNF-R-II,
TNF-R75, TNFBR, TNFR1B,
TNFR2, TNFR80, p75, p75TNFR
191191
TNFRSF3 Chromosome 12, NC_000012.12
(6375160..6391571)
LTBR, D12S370, LT-BETA-R,
TNF-R-III, TNFCR, TNFR-RP,
TNFR2-RP, TNFR3, TNFRSF3
600979
TNFRSF4 Chromosome 1, NC_000001.11
(1211326..1216812,
complement)
ACT35, CD134, IMD16, OX40, TXGP1L 600315
TNFRSF5 Chromosome 20, NC_000020.11
(46118242..46129858)
CD40, Bp50, CDW40, TNFRSF5, p50 109535
TNFRSF6 Chromosome 10, NC_000010.11
(88968429..89017059)
ALPS1A, APO-1, APT1,
CD951, FASTM, TNFRSF6, FAS
134637
TNFRSF6B Chromosome 20, NC_000020.11
(63696652..63698684)
DCR3, DJ583P15.1.1,
M68, M68E, TR6
603361
TNFRSF7 Chromosome 12, NC_000012.12
(6444867..6451718)
CD27, S152, S152. LPFS2,
T14, TNFRSF7, Tp55
186711
TNFRSF8 Chromosome 1, NC_000001.11
(12063303..12144213)
CD30, D1S166E, Ki-1 153243
TNFRSF9 Chromosome 1, NC_000001.11
(7915871..7941607,
complement)
4-1BB, CD137, CDw137, ILA 602250
TNFRSF10A Chromosome 8, NC_000008.11
(23190452..23225102,
complement)
APO2, CD261, DR4,
TRAILR-1, TRAILR1
603611
TNFRSF10B Chromosome 8, NC_000008.11
(23020133..23069031, complement)
CD262, DR5, KILLER,
KILLER/DR5, TRAIL-R2, TRAILR2,
TRICK2, TRICK2A, TRICK2B,
TRICKB, ZTNFR9
603612
TNFRSF10C Chromosome 8, NC_000008.11
(23102921..23117445)
CD263, DCR1, DCR1-TNFR,
LIT, TRAIL-R3, TRAILR3, TRID
603613
TNFRSF10D Chromosome 8, NC_000008.11
(23135588..23164027, complement)
CD264, DCR2, TRAIL-R4,
TRAILR4, TRUNDD
603614
TNFRSF11A Chromosome 18, NC_000018.10
(62325310..62391288)
CD265, FEO, LOH18CR1,
ODFR,OFE, OPTB7, OSTS,
PDB2,RANK, TRANCER
603499
TNFRSF11B Chromosome 8, NC_000008.11
(118923557..118951885,
complement)
OCIF, OPG, PDB5, TR1 602643
TNFRSF12A Chromosome 16, NC_000016.10
(3020368..3022383)
CD266, FN14, TWEAKR 605914
TNFRSF13B Chromosome 17, NC_000017.11
(16939081..16972118, complement)
CD267, CVID, CVID2,
IGAD2, RYZN, TACI,
TNFRSF14B
604907
TNFRSF13C Chromosome 22, NC_000022.11
(41922032..41926806, complement)
BAFF-R, BAFFR, BROMIX,
CD268, CVID4, prolixin
606269
TNFRSF14 Chromosome 1, NC_000001.11
(2556371..2563829)
ATAR, CD270, HVEA,
HVEM, LIGHTR, TR2
602746
TNFRSF16 Chromosome 17, NC_000017.11
(49495293..49515008)
NGFR, CD271, Gp80-LNGFR,
TNFRSF16, p75(NTR), p75NTR
162010
TNFRSF17 Chromosome 16, NC_000016.10
(11965210..11968068)
BCM, BCMA, CD269,
TNFRSF13A
109545
TNFRSF18 Chromosome 1, NC_000001.11
(1203508..1207901, complement)
AITR, CD357, ENERGEN,
GITR, GITR-D
603905
TNFRSF19 Chromosome 13, NC_000013.11
(23570248..23676093)
TAJ, TAJ-alpha,
TRADE, TROY
606122
TNFRSF19L Chromosome 11, NC_000011.10
(73376395..73397474)
RELT, AI3C,
TNFRSF19L, TRLT
611211
TNFRSF21 Chromosome 6, NC_000006.12
(47231532..47309910, complement)
BM-018, CD358, DR6 605732
TNFRSF25 Chromosome 1, NC_000001.11
(6460786..6466173, complement)
APO-3, DDR3, DR3,
GEF720, LARD, PLEKHG5,
TNFRSF12, TR3, TRAMP,
WSL-1, WSL-LR
603366
TNFRSF27 Chromosome X, NC_000023.11
(66594384..66639303, complement)
EDAR2, EDA-A2R,
EDAA2R, TNFRSF27, XEDAR
300276
EDAR Chromosome 2, NC_000002.12
(108894471..108989256,
complement)
EDAR, DL, ECTD10A,
ECTD10B, ED1R, ED3,
ED5, EDA-A1R, EDA1R,
EDA3, HRM1
60409



表4. 小鼠中TNF受体超家族成员
 

Name Location Aliases
TNFRSF1A Chromosome 6, NC_000072.7
(125326686..125339446)
CD120, CD120a, FPF, TN, TNF-,
TNF-R, TNF-R-I, TNF-R1, TNF-R55,
TNF-a, TNF-alphaR1, TNFAR, TNFR,
TNFR60, TNFRI, TNFRp55, TNFal,
TNFalpha-R1, Tnf, Tnfr-2,
Tnfr1, p5, p55, p55-R
TNFRSF1B Chromosome 4, NC_000070.7
(144938938..144973453, complement)
CD120b, TN, TNF-, TNF-R,
TNF-R-II, TNF-R2, TNF-R75,
TNF-a, TNF-alphaR2, TNFBR,
TNFR, TNFR80, TNFRII, TNFal,
TNFalpha-R2, Tnf, Tnfr-1,
Tnfr2, p7, p75
TNFRSF3 Chromosome 6, NC_000072.7
(125283534..125291026, complement)
Ltbr, AI256028, L, LTbe,
LTbetaR,Ltar, TN, TNF-,
TNF-R-III,TNFCR, TNFR,
TNFR-RP,TNFR2-RP, TNFRrp,
Tnf,Tnfbr, Tnfrsf3
TNFRSF4 Chromosome 4, NC_000070.7
(156098049..156101070)
ACT3, ACT35, CD134,
Ly-70, Ox4, Ox40,
TXGP1L, Txgp, Txgp1
TNFRSF5 Chromosome 2, NC_000068.8
(164897535..164913574)
CD40, AI326936, Bp5,
Bp50, GP39, HIGM1,
IGM, IMD3, T-BAM,
TRAP, Tnfr, Tnfrsf5, p5, p50
TNFRSF6 Chromosome 19, NC_000085.7
(34267926..34305175)
Fas, AI196731, AP, APO1,
APT1, CD95, TNF, TNFR6,
Tnfr, Tnfrsf6, lpr
TNFRSF7 Chromosome 6, NC_000072.7
(125209583..125214014, complement)
CD27, S15, S152,
Tnfr, Tnfrsf7, Tp5, Tp55
TNFRSF8 Chromosome 4, NC_000070.7
(144993702..145041734, complement)
Cd30, D1S166E, Ki, Ki-1
TNFRSF9 Chromosome 4, NC_000070.7
(151004612..151030561)
4-1BB, A930040I11Rik,
AA408498, AI325004, CDw137,
Cd137, ILA, Ly6, Ly63
TNFRSF10B Chromosome 14, NC_000080.7
(70004921..70021860)
DR, DR5, KI, KILLER,
Kille, Ly9, Ly98, MK, TR, TRA,
TRAILR2, TRIC, TRICK,
TRICK2A, TRICK2B, TRICKB
TNFRSF11A Chromosome 1, NC_000067.7
(105708448..105777172)
Ly109, ODFR, OFE, R,
Rank, TRAN,
TRANCE-R,mRANK
TNFRSF11B Chromosome 15, NC_000081.7
(54114014..54141880, complement)
O, OC, OCIF, Opg, TR, TR1
TNFRSF12A Chromosome 17, NC_000083.7
(23894419..23896423, complement)
AI255180, C87282, Fn1,
Fn14, HPIP, TWEAK,
TWEAK-R, Twea, TweakR
TNFRSF13B Chromosome 11, NC_000077.7
(61017567..61040435)
1200009E08Rik, Ta, Taci
TNFRSF13C Chromosome 15, NC_000081.7
(82105943..82108581, complement)
2010006P15Rik, BAFF,
BAFF-R,Baf, Baffr, Bcmd,
Bcmd-1,Bcmd1, Lv, Lvis22
TNFRSF14 Chromosome 4, NC_000070.7
(155002944..155013077, complement)
A, Atar, Hv, Hve,
HveA, Hvem,
TR2, Tnfrs14
TNFRSF16 Chromosome 11, NC_000077.7
(95459644..95478524, complement)
Ngfr, LN, LNGFR, Tnfrs,
Tnfrsf16, p7, p75,
p75N, p75NGFR, p75NTR
TNFRSF17 Chromosome 16, NC_000082.7
(11131131..11137938)
BCM, BCMA, Tnfrs,
Tnfrsf13, Tnfrsf13a
TNFRSF18 Chromosome 4, NC_000070.7
(156110779..156113351)
AITR, Gi, Gitr
TNFRSF19 Chromosome 14, NC_000080.7
(61201283..61284304, complement)
AL023044, AW123854, TA,
TAJ, TAJ-, TAJ-ALPHA,
TRA, TRADE, Tr, Troy
TNFRSF19l Chromosome 7, NC_000073.7
(100495054..100512690, complement)
Relt, E430021K24Rik,
Tnfrs, Tnfrsf19i
TNFRSF21 Chromosome 17, NC_000083.7
(43327446..43400079)
AA959878, DR, DR6,
R74815, TR, TR7
TNFRSF22 Chromosome 7, NC_000073.7
(143188545..143203412, complement)
2810028K06Rik, C130035G06Rik,
S, SOBa, Tnfr, Tnfrh2,
Tnfrsf1al2, mDcTr, mDcTrailr2
TNFRSF23 Chromosome 7, NC_000073.7
(143219544..143239836, complement)
SOB, TNFRSFH23, Tnfr, Tnfrh1,
Tnfrsf1al1, mDcTRAILR1,
mDcTr, mS, mSOB
TNFRSF24 Chromosome 7, NC_000073.7
(143161422..143181690, complement)
Tnfr, Tnfrh3, Tnfrsf26
TNFRSF25 Chromosome 4, NC_000070.7
(152199985..152204576)
AP, APO-3, DDR, DDR3, DR, DR3, L,
LARD, TR, TR3, TRAMP, Tnfrs,
Tnfrsf12, W, WS, WSL-1, WSL-LR, Wsl
TNFRSF27 Chromosome X, NC_000086.8
(96377447..96420815, complement)
EDA2R, 9430060M22Rik,
TNFRSF27, Xed, Xedar
Edar Chromosome 10, NC_000076.7
(58436602..58511518, complement)
EDAR, ED1R, ED3, ED5,
EDA-A1R, EDA3, dl
 

多数配体形成非共价同源三聚体,但Ltβ(TNFSF3)与TNFβ(TNFSF1)形成异源三聚体,BAFF(TNFSF13B)与APRIL(TNFSF13)形成异源三聚体。TNF配体是膜锚定或可溶性三聚体,一般来说,一个三聚体配体与三个单体受体结合,激活细胞内信号通路。通过基于系统流式细胞术的分析,Bossen等人证明了调节小鼠和人类TNFSF–TNFRSF相互作用的机制。他们发现TNFSF配体与一到五种不同的受体结合,而大多数受体与一到三种配体结合。特别注意的是,他们观察到,尽管含有经典的CRD结构,但DR6(TNFRSF21)、RELT(TNFRSF19l)、TROY(TNFRSF19)和神经生长因子受体(NGFR,TNFRSF16)没有与任何TNFSF结合,因此表明它们要么与其他配体结合,要么以配体独立的方式发挥作用。后来的研究表明,NGFR结合了一种结构上不同的配体——神经营养素。

TNF超家族受体及配体结合情况见图1.
 

图1. TNF超家族配体与受体之间的相互作用。TNF配体(左)和TNF受体(右)在两个独立但相互作用的细胞上表现为跨膜蛋白。垂直虚线代表这些细胞的质膜。LTα3(TNFSF1同源三聚体)不以膜结合形式出现并且可溶。DcR1通过脂质(GPI)锚定在质膜上。

 

二、 TNF超家族功能


许多TNFRSF分子表达在免疫系统的细胞中,他们参与B细胞、T细胞、DK细胞等的发育、成熟、内稳态、活化、存活、分化;影响B细胞表达抗原或免疫反应调节因子的能力;参与淋巴组织的发育等过程(表5)。然而,它们的功能并不局限于免疫细胞,还与一系列病理生理有关,包括癌症、神经系统疾病、心血管疾病、肺疾病、自身免疫疾病和代谢疾病等,而且具有“双刃剑”的特性(图2,3)。

 

表5. TNF超家族成员的免疫学功能(摘自文献4)



图2. TNF家族分子与炎症和自身免疫性疾病的发生有关(摘自文献6)。


该图是使用TNF家族配体/受体缺乏的小鼠和/或用配体或受体的中和抗体治疗的野生型小鼠的数据汇编而成。

 

图3 TNF超家族成员的主要生理和病理效应。

 

不同的研究表明,尽管肿瘤坏死因子(TNF)及其超家族成员对造血、防止细菌感染、免疫监视和肿瘤消退(以绿色表示)至关重要,但其失调会导致各种疾病(以蓝色表示)。这种“双刃剑”的角色是肿瘤坏死因子超家族大多数成员的典型特征。


因此,一些以TNF或TNFR超家族分子为靶点的生物制剂正在进行自身免疫性、炎症性疾病和癌症的临床试验。TNF家族成员仍将是研究热点。


内容主要摘自:

1. Ware CF. The TNF Superfamily-2008. Cytokine Growth Factor Rev. 2008. 19(3-4):183-6.

2. Dostert C et al. The TNF Family of Ligands and Receptors: Communication Modules in the Immune System and Beyond. Physiol Rev. 2019. 99(1):115-160.

3. Sandip Sonar et al. Role of tumor necrosis factor superfamily in neuroinflammation and autoimmunity. Front. Immunol., 2015. https://doi.org/10.3389/fimmu.2015.00364

4. Tafalla C, et al. Novel Insights on the Regulation of B Cell Functionality by Members of the Tumor Necrosis Factor Superfamily in Jawed Fish. Front Immunol. 2018. 9:1285.

5. Bharat B Aggarwal. Signaling pathways of the TNF superfamily: a double-edged sword. Review Nat Rev Immunol. 2003 Sep;3(9):745-56.

6. Michael Croft et al. TNF superfamily in inflammatory disease: translating basic insights. Review Trends Immunol. 2012. 33(3):144-52.

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