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@carlosarangof @MasatoOgishi @DelmonteOttavia @AhmadYatim_ @ANDRESF06942225 @Jonathan_Bohlen @Linndred @AntoineFayand @JPsico1989 @JulianRojasSilv @YSeeleuthner @PhilippotQ @grvsadrian @lulabovary @alejogallon @JeanMarcDoisne @Jaalvarez9A @EstefyVasquezE @Marce_MoncadaV @juanalvaro250 @palterer @pjpatino63 @MChaldebas @zhangpeng1202 @DrCindyMa @JfarMde @DRinchai @Boisson_Bebo @_nicomarr @BoissonDupuis @KiritsiDimitra @BenedicteNeven @LaurentAbel4 @andrealisco1 @BeziatV @HHMINEWS @RockefellerUniv @Inserm @univ_paris_cite @InstitutImagine @APHP @NIAIDNews @ncats_nih_gov @FisherCenter @SNForg 17) @Creches_LPCR, @ESIDsociety, @UdeA, @MincienciasCo, @FundacionFIP, St. Giles Foundation, BBAG, and WE Ford, G Caillaux & General Atlantic Foundation!.

@carlosarangof @MasatoOgishi @DelmonteOttavia @AhmadYatim_ @ANDRESF06942225 @Jonathan_Bohlen @Linndred @AntoineFayand @JPsico1989 @JulianRojasSilv @YSeeleuthner @PhilippotQ @grvsadrian @lulabovary @alejogallon @JeanMarcDoisne @Jaalvarez9A @EstefyVasquezE @Marce_MoncadaV @juanalvaro250 @palterer @pjpatino63 @MChaldebas @zhangpeng1202 @DrCindyMa @JfarMde @DRinchai @Boisson_Bebo @_nicomarr @BoissonDupuis @KiritsiDimitra @BenedicteNeven @LaurentAbel4 @andrealisco1 @BeziatV 16/ We would also like to extend a special thank you to our funders: @hhminews, @rockefelleruniv, @inserm, @univ_paris_cite, @InstitutImagine, @APHP, @NIAIDnews, @ncats_nih_gov, @FisherCenter, @SNForg, @AgenceRecherche, @FRM_officiel, @HorizonEU, @FduSouffle, @SQUARE_management,.

@carlosarangof @MasatoOgishi @DelmonteOttavia @AhmadYatim_ @ANDRESF06942225 @Jonathan_Bohlen @Linndred @AntoineFayand @JPsico1989 @JulianRojasSilv @YSeeleuthner @PhilippotQ @grvsadrian @lulabovary @alejogallon @JeanMarcDoisne @Jaalvarez9A @EstefyVasquezE @Marce_MoncadaV @juanalvaro250 @palterer @pjpatino63 @MChaldebas @zhangpeng1202 @DrCindyMa @JfarMde @DRinchai @Boisson_Bebo @_nicomarr @BoissonDupuis @KiritsiDimitra @BenedicteNeven @LaurentAbel4 @andrealisco1 @BeziatV @JouanguyE @BustamanteJaci1 @TurveyLab @R_cheynier @maiysha2000 15) @AriasAAS, @FrancoJL_UDEA, @casanova_lab, and those not on twitter.

@carlosarangof @MasatoOgishi @DelmonteOttavia @AhmadYatim_ @ANDRESF06942225 @Jonathan_Bohlen @Linndred @AntoineFayand @JPsico1989 @JulianRojasSilv @YSeeleuthner @PhilippotQ @grvsadrian @lulabovary @alejogallon @JeanMarcDoisne @Jaalvarez9A @EstefyVasquezE @Marce_MoncadaV @juanalvaro250 @palterer @pjpatino63 14) @Mchaldebas, @zhangpeng1202, @DrCindyMa, @JfarMde, @Drinchai, @Boisson_Bebo, @_nicomarr, @BoissonDupuis, @KiritsiDimitra, @BenedicteNeven, @LaurentAbel4, @andrealisco1, @BeziatV, @JouanguyE, @BustamanteJaci1, @TurveyLab, @ldnotar, @R_cheynier, @maiysha2000,.

@carlosarangof @MasatoOgishi @DelmonteOttavia @AhmadYatim_ @ANDRESF06942225 13) @Jonathan_Bohlen, @Linndred, @AntoineFayand, @Jpsico1989, @JulianRojasSilv, @Yseeleuthner, @PhilippotQ, @grvsadrian, @lulabovary, @alejogallon, @JeanMarcDoisne, @Jaalvarez9A, @EstefyVasquezE, @Marce_MoncadaV, @juanalvaro250, @palterer, @pjpatino63,.

12) We are incredibly grateful to the patients and their families, as well as the brilliant collaborators and colleagues from around the world who made this study possible: @carlosarangof, @MasatoOgishi, @DelmonteOttavia, @AhmadYatim_, @ANDRESF06942225.

11) They thus hint that another IL-7R-binding cytokine, possibly thymic stromal lymphopoietin (TSLP), might support an IL-7-independent pathway of human T cell development. 🔬.

10) Our findings suggest that human IL-7 deficiency does not affect T cell development as profoundly as IL-7R deficiency (.

9) Strikingly, IL-7-deficient mice have a profound reduction of αβ T cells, an absence of γδ T cells, and markedly reduced B cell counts (, differing from human IL-7 deficiency (.

8) Interestingly, effector memory CD4+ and CD8+ T cell proportions were high, while other T cell subsets like TCRγδ T cells, Th1, Tfh, and Treg cells were minimally impacted.

7) IL-7 deficient patients also had low TCR excision circles (TRECs), recent thymic emigrant T (RTE) and naive CD4+ T cells, along with reduced overall TCR repertoire diversity, indicating impaired thymic output.

6) Deep immunophenotyping revealed near-normal levels of myeloid, B, NK, and innate lymphoid cells. However, they had a T cell lymphopenia, and low frequencies of MAIT and invariant NK T cells.

5/ Surprisingly they display combined immunodeficiency but not SCID.

4/ We now report 6 adults (ages 22-59) from 4 kindreds across 3 ancestries (Colombian, Israeli Arab, Japanese) who are homozygous for IL7loss-of-function variants.

3/ In 1998, I reported as a post-doc with Warren Leonard, in collaboration with Rebecca H. Buckley, that infants with biallelic deleterious IL7Rvariants develop SCID (T–B+NK+) – this is to say that IL-7 is dear to my heart 🙂 (.

2/ Graphical abstract