Schlafens tuaj yeem tso cov kab mob kom tsaug zog Part 1

Abstract:

Cov tsev neeg Schlafen encodes cov proteins uas koom nrog hauv ntau yam kev ua haujlwm lom neeg, suav nrog kev loj hlob ntawm tes, kev sib txawv, thiab kev loj hlob T-cell. Schlafens tau pib pom nyob rau hauv nas, thiab tau kawm nyob rau hauv cov ntsiab lus ntawm kev mob qog noj ntshav, nrog rau lawv lub luag haujlwm hauv kev tiv thaiv cov hlwb thaum kis kab mob. Cov tsev neeg protein no muab cov kab mob tiv thaiv kab mob los ntawm kev cuam tshuam ncaj qha thiab tsis ncaj rau tus kab mob. Schlafens tuaj yeem cuam tshuam cov kab mob sib kis nrog RNA thiab DNA genomes. Hauv qhov kev tshuaj xyuas no, peb nthuav tawm cov haujlwm ntawm tes thiab kev sib raug zoo ntawm Schlafens thiab kev tiv thaiv hauv lub cev. Peb kuj tham txog kev ua haujlwm thiab kev sib txawv ntawm tsev neeg cov proteins uas tau tshwm sim los ua tus tswv tsev txwv tsis pub kis tus kab mob. Kev tshawb fawb ntxiv rau hauv Schlafen protein muaj nuj nqi yuav muab kev pom rau hauv cov txheej txheem uas ua rau muaj kev tiv thaiv kab mob hauv lub cev thiab lub cev.

Gene tsev neeg cov cai muaj feem xyuam nrog kev tiv thaiv kab mob. Ntau tsev neeg gene encode cov proteins thiab molecules uas sawv cev rau lub cev tiv thaiv kab mob tshwj xeeb uas ua haujlwm zoo ua ke los koom tes thiab qhib lub cev tiv thaiv kab mob.

Ib tsev neeg tseem ceeb tshaj plaws yog tsev neeg immunoglobulin, tseem hu ua immunoglobulin superfamily. Tsev neeg no encodes ib tug series ntawm immunoglobulin molecules, xws li IgG, IgM, IgA, IgE, thiab IgD. Cov immunoglobulin molecules no tuaj yeem khi cov antigens txawv teb chaws thiab ua kom lub cev tiv thaiv kab mob. Tsis tas li ntawd, cov tswv cuab ntawm tsev neeg immunoglobulin tseem tuaj yeem qhib thiab tswj cov haujlwm ntawm lub cev tiv thaiv kab mob los ntawm kev khi rau cov receptors ntawm qhov chaw ntawm lub cev tiv thaiv kab mob.

Lwm tsev neeg tseem ceeb yog tib neeg leukocyte antigen (HLA) tsev neeg, tseem hu ua histocompatibility complex. Cov tsev neeg no encodes tib neeg leukocyte antigens, uas muaj nyob rau hauv tib neeg cov ntaub so ntswg loj thiab tuaj yeem paub thiab khi txawv teb chaws antigens thiab muab tso rau hauv T hlwb hauv lub cev tiv thaiv kab mob, yog li ua rau lub cev tiv thaiv kab mob.

Tsis tas li ntawd, muaj ntau lwm cov noob caj noob ces encoding cov proteins uas cuam tshuam txog kev tiv thaiv kab mob, xws li tsev neeg chemokine, nitrite synthase tsev neeg, thiab lwm yam.

Yog li ntawd, cov proteins encoded los ntawm tsev neeg cov noob yog qhov tseem ceeb rau kev tswj lub cev tiv thaiv kab mob thiab txhawb kev tiv thaiv kab mob. Kev hloov pauv lossis kev hloov pauv hauv qee cov noob tuaj yeem ua rau lub cev tsis muaj zog, ua rau muaj kab mob xws li kab mob autoimmune, kab mob tiv thaiv kab mob, thiab kab mob sib kis. Yog li ntawd, kev kawm txog kev sib raug zoo ntawm cov noob tsev neeg coding thiab kev tiv thaiv kab mob yog qhov tseem ceeb heev rau kev tiv thaiv thiab kho cov kab mob no. Yog li ntawd, peb yuav tsum tau xyuam xim tshwj xeeb rau kev txhim kho peb txoj kev tiv thaiv. Cistanche tuaj yeem txhim kho kev tiv thaiv kab mob, thiab cov polysaccharides hauv cov nqaij tuaj yeem tswj lub cev tiv thaiv kab mob ntawm tib neeg lub cev, txhim kho kev ntxhov siab ntawm lub cev tiv thaiv kab mob, thiab txhim kho cov kab mob bactericidal ntawm lub cev tiv thaiv kab mob.

Nyem cistanche deserticola ntxiv

Ntsiab lus:

Schlafen; SLFN; innate kev tiv thaiv; kab mob vais lav; txwv qhov tseem ceeb; tiv thaiv evasion.

1. Taw qhia

Xyoo 1998, Schlafen (SLFN rau tib neeg; Slfn rau nas) noob tau tshaj tawm thawj zaug hauv kev tshawb fawb ntawm murine thymus txoj kev loj hlob. Thawj Schlafens pom yog murine noob Slfn1-4. Thaum Slfn1 qhia ectopically hauv NIH-3T3 fibroblasts, nws induces G0/G1 cell voj voog ntes; Qhov kev soj ntsuam no tau coj mus rau lub txiaj ntsig ntawm lo lus "schlafen" los ntawm lo lus German lub ntsiab lus "mus pw" [1].

Cov kev tshawb fawb tom qab pom tias Schlafens ua lub luag haujlwm hauv ntau lub zog ntawm tes, suav nrog kev tiv thaiv kev loj hlob thiab kev sib txawv ntawm tes [2-7], kev txav chaw qog nqaij hlav qog noj ntshav, kev loj hlob, thiab kev tiv thaiv kev ntxeem tau [8-11], rhiab ntawm cov qog nqaij hlav cancer rau DNA-ua puas tsuaj. tshuaj [12–17], thiab inhibition of viral replication [18–24]. Raws li kev tshawb fawb ntawm Schlafen tsev neeg tau nthuav dav nyob rau xyoo tas los no, kev kawm tau zoo tau ua tiav rau kev nkag siab tias cov proteins hauv tsev neeg no muaj kev ua haujlwm zoo li cas. Cov ntawv tshuaj xyuas zoo tsis ntev los no tau piav qhia lawv qhov tseem ceeb rau thaj tsam ntawm kev mob qog noj ntshav [25].

Schlafen proteins kuj muaj lub luag haujlwm hauv kev tswj cov kab mob thiab lub cev tiv thaiv kab mob. Ntawm no, peb hais txog kev ua haujlwm zoo sib xws thiab qhov sib txawv ntawm Schlafen cov neeg hauv tsev neeg hais txog lawv lub luag haujlwm hauv kev tswj hwm tus kab mob thiab kev tiv thaiv kab mob. Cov kev tshawb pom tsis ntev los no txhawb cov kev tshawb fawb yav tom ntej rau hauv tsev neeg muaj protein ntau.

2. Schlafen Tsev Neeg thiab Protein Composition

Schlafen gene tsev neeg muaj ntau homologous thoob plaws ntau hom tsiaj. Nine Schlafen proteins yog qhia nyob rau hauv nas los ntawm chromosome 11, thiab rau tau pom nyob rau hauv tib neeg los ntawm chromosome 17 (Daim duab 1) [3,26]. Txawm hais tias Slfn-zoo li 1 (Slfn1L) tau hais tawm ntawm nas chromosome 4, muaj kev xav tias nws tsis suav tias yog 'bona file Schlafen tsev neeg vim qhov tsis tshua muaj qhov zoo sib xws rau Slfn noob [26,27]. Tsis tas li ntawd, Slfn6 thiab Slfn7 raug suav hais tias yog cov khoom sib txuas tau los ntawm Slfn3 lossis Slfn4 isoforms lossis lwm cov nas paralogues [1,27].

Schlafen cov tswv cuab poob rau hauv peb pawg sib txawv, txhua tus muaj nws qhov tshwj xeeb ntawm cov yam ntxwv thiab kev ua haujlwm (Daim duab 1). Pawg I muaj qhov sib txawv AAA ATPase-txuas nrog cov npe uas muaj thaj tsam Slfn-box uas tau raug hu ua Schlafen core domain, thiab tau koom nrog ob pawg [2,28–31]. Schlafen core domain yog horseshoe zoo li tus thiab muaj zinc ntiv tes motifs uas tau txais kev cawmdim hauv txhua tus tswv cuab ntawm Schlafen tsev neeg cov proteins.

Pawg II thiab III muaj qhov txuas ntxiv txuas ntxiv tom qab Schlafen core domain, uas yog qhov chaw nyob ntawm SWADL motif uas txhais los ntawm cov amino acid ib ntus qauv SW-(A/S)-(V/G/L)-D-(L/I/ V) nrog tsis paub ua haujlwm [3,29]. Tsuas yog pawg III cov proteins muaj qhov txuas ntxiv carboxyl (C)-ib lub davhlau ya nyob twg uas sib tw superfamily I ntawm DNA / RNA helicases [2]. Schlafen core domain tsis muaj Walker motif. Lub Walker A thiab B sawv cev rau cov qauv tsim rau nucleotide khi thiab tau pom nyob rau hauv AAA tsev neeg ntawm ATPases [32].

Vim tias tsis muaj Walker motifs, Schlafen proteins hauv pawg I thiab II yuav tsis muaj ATPase kev ua. Putative DNA / RNA helicase domains ntawm qee pab pawg III Schlafen cov tswv cuab muaj AAA domains nrog Walker motifs uas zoo li ua rau muaj zog ua haujlwm [18,33,34]. Cov no tsis tiav hauv murine thiab tib neeg Schlafen 14, uas muaj tsuas yog Walker B motif [31]. Tsis tas li ntawd, C-terminal txuas ntxiv ntawm qee pawg III Schlafens muaj lub teeb liab hauv cheeb tsam nuclear (NLS) thiab tej zaum yuav muaj kev ua haujlwm nuclear (Daim duab 1) [20,24,25]

Tsuas yog cov platypus, ib tug monotreme, Schlafen tsev neeg muaj nyob rau hauv xyaum tag nrho cov tsiaj. Sequences zoo ib yam li Schlafen noob tau pom nyob rau hauv amphibian Xenopus laevis thiab cov ntses hom Callorhincuys milii, tab sis tsis nyob rau hauv lwm yam uas tsis yog-niam txiv kab mob. Interestingly, sequences zoo li Schlafens tau pom los ntawm bioinformatic tsom xam ntawm genomes rau orthopoxvirus (OPV), xws li tshuaj tiv thaiv, variola (smallpox), thiab cowpox viruses [1]. Tom qab kev sib txuas ntawm tus kab mob camelpox (CMLV) tau txheeb xyuas lwm cov protein zoo li Schlafen hu ua 176R. Cov protein no muaj 502 amino acids thiab muaj C-terminal ib ntus uas piv rau Schlafen core domain ntawm murine Schlafens. Qee tus kab mob Schlafen (v-Slfn) cov noob khaws cia tag nrho qhib kev nyeem ntawv (ORF).

Thaum ORF rau v-Slfn tsis zoo nyob rau hauv cov genomes ntawm camelpox, monkeypox, cowpox, mousepox, thiab taterapox viruses, protein qhia yog txwv nyob rau hauv lwm yam OPVs, xws li cov tshuaj tiv thaiv kab mob (VACV), vim ORF fragmentation [1,26 , 35] ib. Cov kab ke ntawm v-Slfn tau pom tias zoo ib yam li nas thiab nas pawg I Schlafen, tab sis tsis muaj C-terminal domain. Qhov no txhais tau hais tias, thaum tus kab mob progenitor ntawm OPV tuaj yeem tau txais Schlafen tsis zoo los ntawm cov nas, ORF tau tawg vim yog kev hloov pauv tau dhau sijhawm [26,27].

3. Kev Cai Qhia Txog Schlafens hauv Kev Tiv Thaiv Kab Mob

Schlafen cov neeg hauv tsev neeg tau raug qhia tias raug ntxias los ntawm ntau qhov kev xav, suav nrog CpG-DNA [36], LPS [36–38], thiab cov kab mob, xws li Brucella, Listeria [39], thiab rhinovirus [37]. Hom I IFN thiab IFN receptors tau raug cuam tshuam rau hauv induction ntawm Schlafen noob, hais tias Schlafens yog IFN-stimulated noob (ISGs). Hauv xyoo 2010, nws tau tshaj tawm thawj zaug tias IFN cuam tshuam rau kev qhia ntawm cov tswv cuab ntawm Schlafen gene tsev neeg [40]. Cov ntaub ntawv nthuav tawm hauv qhov kev tshawb fawb no qhia tias hom I IFN yog ib qho muaj zog inducer ntawm ntau tus nas Schlafen tsev neeg, suav nrog cov tswv cuab ntawm pawg I (Slfn1 thiab Slfn2), pawg II (Slfn3), thiab pawg III (Slfn5 thiab Slfn8). IFN-activated Stat proteins thiab p38 MAP kinase ua haujlwm sib txawv hauv lawv cov kev cai ntawm interferon-induced qhia [41].

Nyob rau hauv Stat1 deletion nyob rau hauv nas embryonic fibroblasts, IFN-dependent qhia ntawm tag nrho cov Schlafen noob tau txo tus txheeb ze rau cov niam txiv cov hlwb, xws li los ntawm ib feem yuav txo tau nyob rau hauv Slfn3 mus rau tag nrho transcriptional defects nyob rau hauv Slfn1, 2, 5, thiab 8. Interestingly, Slfn5 qhia tau tag nrho. ywj siab ntawm Stat3, tab sis nws tau nce hauv Stat3 knockout hlwb. Kev ua haujlwm ntawm p38 MAPK-activated signaling cascades yuav tsum tau ua kom tiav kev ua kom tiav ntawm ISGs. Txawm li cas los xij, thaum p38 MAPK xav tau rau IFN-raws li kev qhia ntawm Schlafen noob nyob rau hauv pawg I thiab II, nthuav, pawg III noob qhia tsis yog nyob ntawm p38 MAPK.

Thaum tsis muaj p38 MAPK, IFN-dependent mRNA qhia ntawm Slfn1, Slfn2, thiab rau qhov tsawg dua Slfn3, raug txwv. Pawg III Schlafen noob, SLFN5 thiab SLFN8, ntawm qhov tod tes, raug ntxias los ntawm IFN hauv p38 MAPK-kev ywj pheej [41]. Qhov tseem ceeb, tsis yog Stat3 lossis p38 MAPK yog qhov tsim nyog rau Slfn5 induction, qhia tias lwm txoj kev tswj hwm tau koom nrog hauv cov txheej txheem no.

Qhov induction ntawm ISGs los ntawm hom I IFNs yuav tsum muaj cov ntsiab lus ntawm interferon-stimulated teb (ISREs) nyob rau hauv cheeb tsam txhawb nqa ntawm ISG, uas ua rau transcriptional activation los ntawm kev khi ntawm ISGF3 transcription factor, complex ntawm phosphorylated STAT1 / STAT2 heterodimers, thiab IRF9 [42]. Lub inducibility ntawm Schlafens los ntawm IFN los yog IFN stimuli yog qis dua rau MxA, ib tug pa ISG [37].

Kev tshuaj xyuas ntawm qhov chaw sib txuas lus sib txuas siv qhov kev pab cuam MatInspector [43] pom tias MxA muaj rau ISRE qhov chaw, thaum tib neeg Schlafen noob feem ntau tsuas muaj ib qho canonical ISRE [37]. Txawm hais tias tsev neeg Schlafen koom nrog cov pab pawg ntawm ISGs classical tswj los ntawm STAT complex, qee qhov Schlafens tau hais los ntawm txoj hauv kev uas tsis yog IFN lossis cov txheej txheem tsis tau txhais. Muaj ntau theem ntawm Schlafens tau qhia nyob rau hauv ntau lub hlwb, nrog rau thawj fibroblasts thiab qog nqaij hlav cancer, thaum tsis muaj IFN ua kom [18,20,44].

Lub rhiab heev ntawm Schlafen qhia rau IFN txawv raws li hom ntawm tes. Piv txwv li, SLFN5 kev qhia yog suppressed nyob rau hauv malignant melanoma piv rau ib txwm melanocytes. IFN stimulation, ntawm qhov tod tes, nce SLFN5 kev nthuav qhia, thaum SLFN11, SLFN12, thiab SLFN13 tsis cuam tshuam [40]. Nyob rau hauv sib piv, IFN stimulants, xws li poly I: C thiab 50 pppdsRNA, nce Slfn5 qhia me ntsis, tab sis tsis tseem ceeb, nyob rau hauv nas macrophage RAW 264.7 hlwb, whereas Slfn14 qhia tau nce ntau [19].

Nyob rau hauv 50 -flanking cheeb tsam ntawm Slfn2 noob, ib daim qauv ntawm ib tug putative NF-κB binding site thiab ob daim ntawv luam ntawm AP-1 binding sequences. Nws tau raug pom tias CpG-DNA thiab LPS kev kho mob ntawm macrophages yuav tsum muaj kev sib cuam tshuam ntawm NF-κB thiab AP1 hauv cov khoom txhawb nqa [36]. Tshawb xyuas thaj tsam txhawb nqa ntawm Slfn4 nrog JASPAR (jaspar.cgb.ki.se) tau nthuav tawm muaj AP1 thiab PU. 1 binding sequence, nrog rau ob daim ntawv theej ntawm IFN teb cov ntsiab lus STAT1 thiab IRF1 binding sequences [38].

Tsis tas li ntawd, Gli1 khi qhov chaw kuj muaj nyob rau hauv tus txhawb nqa. Gli1, Hedgehog signaling effector, yuav tsum tau ua kom muaj Slfn4 txhawb nqa, uas txhais tau hais tias lub luag haujlwm ntawm Slfn4 yog qhov tseem ceeb hauv cov tsos ntawm macrophages qhia IL1 lossis TNF [45]. Hauv cov qog nqaij hlav cancer, epigenetic inhibition ntawm cov noob qhia ntawm CpG txhawb nqa kob hypermethylation yog ib qho tshwm sim tsis tu ncua [46]. Ntau qhov kev tshawb fawb tau tshaj tawm hypermethylation ntawm SLFN11 gene txhawb nqa [14,46–49]. Kev ua kom ntsiag to ntawm SLFN11 los ntawm kev txhawb nqa CpG kob hypermethylation yog txuas rau kev tiv thaiv ntau dua rau platinum tebchaw rau kev kho mob qog noj ntshav [14]. Hypermethylation ntawm CpG promoter kob inactivates SLFN11 noob qhia.

Qhov no methylation yog catalyzed los ntawm ob lub ntsiab DNA methyltransferases, DNMT1 thiab DNMT3B [14]. Qhov tseeb tias DNMT3B kev qhia hauv monocytes tsawg heev, lossis tsis tshua pom tau [50], tuaj yeem txhais tau tias qib siab ntawm SLFN11 qhia hauv monocytes muaj feem xyuam rau hypermethylation. Nws kuj tseem paub los ntawm cov kab mob hauv nruab nrab B cell sib txawv kev tshawb fawb uas histone modifiers, xws li EZH2 thiab HDACs, tswj cov epigenetic qhia ntawm SLFN11 [48].

Tsis tas li ntawd, SLFN11 kev qhia thiab B cell lineage-specific repressor PAX5 tau pom tias muaj ze li qhov sib txawv zoo sib xws [48]. Lub peev xwm PAX5 khi qhov chaw (GCGTGAC) muaj nyob hauv thaj tsam txhawb nqa ntawm SLFN11, qhia tias PAX5 yuav yog ib qho ntawm cov neeg tawm tsam ntawm SLFN11 hauv B hlwb.

Cov tswv cuab Schlafen tau qhia nyob rau ntau theem ntawm kev txhim kho thymocyte thiab peripheral T-cell ua rau cov nas. Slfn1 thiab Slfn2 tau nce siab thaum lub sijhawm hloov pauv ntawm CD4 thiab CD8 ob-zoo rau ib leeg-zoo maturation theem. Txawm li cas los xij, kev qhia theem ntawm ob lub noob tau txo qis tom qab T cell ua haujlwm [1,2,51]. Slfn3 tau qhia ntau heev nyob rau hauv ib leeg-zoo T hlwb thoob plaws thymocyte txoj kev loj hlob. Slfn3 kuj tau qhia nyob rau theem siab dua hauv ntuj CD4 ntxiv rau CD25 ntxiv rau kev tswj T hlwb dua li hauv CD4 ntxiv rau CD25- hlwb. Slfn3 qhia tau nce hauv CD4 ntxiv rau CD25- T hlwb thaum ua kom tab sis txo qis hauv CD4 ntxiv rau CD25 ntxiv rau T hlwb tom qab ua kom muaj zog tiv thaiv CD3/CD28. TGF- stimulation kuj txo Slfn3 qhia hauv CD4 ntxiv rau T cell subset, qhia tias Slfn3 yuav yog ib qho tshiab cim ntawm T cell ua kom [52]. Slfn4 tau tshawb pom ntxov thiab txo qis thaum lub sij hawm kev loj hlob ntawm thymocyte, qhia qhov txawv tshwm sim rau Slfn1 [1,2].

Slfn4 mRNA qib yog upregulated thaum lub sij hawm macrophage activation, whereas lawv yog downregulated thoob plaws qhov sib txawv. Myelopoiesis cuam tshuam los ntawm kev qhia Slfn4 hauv cov kab mob myeloid, txhais tau hais tias kev txo qis ntawm Slfn4 noob qhia thaum lub sijhawm sib txawv ntawm macrophage yog qhov tseem ceeb, thiab Slfn4 tuaj yeem ua tus hloov kho ntawm cov kab no [38]. Tsis zoo li lwm pawg, Slfn5, 8, 9, thiab 10 hauv pab pawg III tsis hloov ntau npaum li cas thaum lub sij hawm kev loj hlob ntawm thymocyte. Thaum lub sij hawm T cell activation, txawm li cas los xij, muaj ib qho tseem ceeb downregulation ntawm Slfn5 thiab Slfn8 qhia, thaum Slfn9 qhia tau nce thiab Slfn10 qhia tseem nyob tas li [2]. Txij li thaum SLFN14 tau qhia nyob rau theem qis heev hauv T hlwb, nws tsis zoo li yuav txuas rau T cell txoj hmoo [37].

Tib neeg Schlafen tsev neeg kuj cuam tshuam nrog kev tiv thaiv kab mob hauv lub cev thiab T-cell maturation. Tsuas yog rau SLFN14, tag nrho cov tib neeg Schlafen proteins tau qhia ib txwm nyob rau hauv monocytes, monocyte-derived dendritic hlwb (moDCs), thiab T hlwb [37]. Kev qhia theem ntawm SLFN5 hauv T hlwb, thiab SLFN11 hauv monocytes thiab moDCs, yog qhov tseem ceeb heev. Qhov kev qhia ntawm SLFN5 thiab SLFN11 hloov me ntsis thoob plaws kev sib txawv ntawm moDC.

Qhov kev qhia ntawm SLFN12L thiab SLFN13 yog qhov qis qis hauv monocytes thaum so tab sis zoo li tau nce siab thaum sib txawv rau hauv moDCs, qhov SLFN12 qhia tau txo qis [37]. Yog li, kev txo qis thiab kev tswj hwm ntawm txhua tus Schlafen tsev neeg cov protein yuav sawv cev rau cov kev cai sib txawv rau cov proteins no hauv kev ua haujlwm moDC.

Intriguingly, zoo nkaus li muaj kev tswj xyuas cov txheej txheem rau kev tswj xyuas kev hloov pauv hauv Schlafen tsev neeg [53]. Qhov poob ntawm Slfn3 los ntawm knockout txo Slfn4, Slfn8, thiab Slfn9 qhia hauv ileal mucosa thaum nce Slfn1 thiab Slfn5. Tsis tas li ntawd, Slfn3 deficiency txo Slfn4 kev qhia thiab nce Slfn8 thiab Slfn9 kev qhia hauv thymus thiab spleen, qhov chaw tiv thaiv kab mob loj hlob thiab / lossis proliferate [53]. Cov neeg txhawb nqa ntawm txhua tus tswvcuab ntawm tsev neeg Schlafen muaj thaj chaw rau kev khi ntawm Kruppel zoo li qhov tseem ceeb-6 (KLF6) qhov kev hloov pauv.
Cov NFAT-muaj feem xyuam nrog ING4, ZNF333, thiab KLF4, kuj tau kwv yees los khi rau feem ntau Schlafen txhawb nqa. Cov kev hloov pauv no los ntawm tsev neeg KLF ua lub luag haujlwm sib txawv hauv kev sib txawv ntawm lub plab zom mov thiab kev loj hlob thiab muaj cov qauv qhia sib txawv [54]. Qhov no qhia tau hais tias cov tswv cuab ntawm KLF thiab Schlafen cov tsev neeg tuaj yeem muaj cov kev tawm tswv yim uas ua raws li kev tswj hwm ntawm plab hnyuv thiab lub cev tiv thaiv kab mob hauv ntau txoj kev [53].

4. Immunodeficiency ntawm Schlafen Mutants

Nws tau raug pom tias Elektra mutant yog homozygous kev hloov pauv ntawm murine Slfn2 thiab ua rau muaj qhov tsis zoo rau kev kis kab mob thiab kab mob [55]. Qhov kev tuag ntawm cov nas tom qab murine cytomegalovirus (MCMV) kis tau zoo heev piv rau cov nas tswj tsiaj qus [55]. Hauv cov nas nrog Elektra phenotype, CD8 ntxiv thiab CD4 ntxiv rau T lymphocytes tsis nthuav dav. Thaum piv rau cov tsiaj qus, cov hlwb no muaj tus nqi siab dua ntawm apoptosis.

Hauv kev teb rau T cell activation signals, qhov kev hloov pauv no xav tias ua rau apoptosis [9]. Elektra nas kuj tau pom qhov txo qis ntawm T hlwb hauv kev teb rau kev kis tus kab mob lymphocytic choriomeningitis. Elektra T hlwb, zoo ib yam li nyuam qhuav qhib T hlwb, tsis tswj cov cellular quiescence thiab nkag mus rau lub post-mitotic theem. T hlwb poob lawv txoj kev loj hlob thiab tuag nyob rau hauv teb rau proliferation / activation signals, ua rau txo T cell pejxeem nyob rau hauv Elektra mutant nas [9].

Muaj cov lus ceeb toom ntawm tus neeg mob uas muaj qhov loj heterozygous poob ntawm SLFN11, SLFN12, thiab SLFN13 noob ntawm chromosome 17 [56]. Tus neeg mob no tau tshawb pom tias muaj qhov txawv txav hauv T-cell proliferation thiab kev tswj lub voj voog ntawm tes. Interestingly, tus neeg mob muaj tus ncej puab qaum Merkel cell carcinoma, ib yam ntawm cov carcinoma txuam nrog ib tug kab mob kis, thiab tau raug suav hais tias yuav raug mob cancer, tau kuaj pom tias muaj T cell lymphoma.

Tus neeg mob cov ntshav thiab ntshav muaj ntau yam kab mob Epstein-Barr thiab Torque teno virus DNA, qhia tias tus neeg mob muaj kev pheej hmoo rau kis kab mob. Tus neeg mob tau muaj CD4 ntxiv / CD8 ntxiv rau lub cev tiv thaiv kab mob thiab kev faib tawm ntawm cov hlwb tsis zoo thiab kev nco, tab sis muaj qhov tsis zoo ntawm T cell proliferation thiab ntau dhau T cell tuag [56].

Kev hloov pauv hauv SLFN14 tau txuas rau macrothrombocytopenia thiab los ntshav ntau dhau [57–61]. Tsis tas li ntawd, platelet muaj nuj nqi txo qis hauv cov neeg mob nrog cov kev hloov pauv no [61]. Qhov kev hloov pauv SLFN14 no nthuav tawm ib hom phenotype tshwj xeeb, nrog platelet txawv txav hauv tib neeg thiab microcytic erythrocytosis hnyav hauv nas [62].

Yog li, SLFN14 tej zaum yuav yog ib qho tseem ceeb hauv cov tsiaj txhu hematopoiesis thiab tuaj yeem ua lub luag haujlwm hauv kev txiav txim siab platelet thiab erythroid kab mob kev cog lus hauv qee hom. Tsis tas li ntawd, cov platelets tam sim no paub tias muaj lub luag haujlwm hauv ntau yam hauv lub cev thiab hloov kho lub cev tiv thaiv kab mob, uas mus deb dhau qhov kev xav ntawm cov platelets tsuas yog cov tshuaj hemostatic thiab thrombolytic nkaus xwb [63]. Yog li, nws tuaj yeem pom tau tias SLFN14 muaj kev cuam tshuam loj heev hauv kev tiv thaiv kab mob los ntawm kev tsim cov platelet thiab kev tswj hwm kev ua haujlwm.

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