working on tuberculosis in the @casanova_lab ! Finding its genetic causes!!!.

15/ @FRM_officiel and @SCOR_SE, and WE Ford, G Caillaux & General Atlantic Foundation.

14/ All this work would not have been possible without generous fundings, particularly from grants from the St. Giles Foundation, @rockefelleruniv, @inserm, @hhminews, @univ_paris_cite, @InstitutImagine, @NIAIDNews, @ncats_nih_gov, @AgenceRecherche, @FRM_officiel, @agenceANRS….

13/ Special thanks also to the clinical teams, and the patients and their families.

12/ @DelmonteOttavia, @Jonathan_Bohlen, @IrisFagniez, @pelham_simon, @weitelei, @DrSeanRiminton, @TurveyLab, @_nicomarr, @AurelieCobat, @DrCindyMa, @LaurentAbel4, @anne_puel, @BustamanteJaci1, @Tangye_Lab, @casanova_lab and those not yet on twitter.

11/ @MasatoOgishi did most of this work during his PhD in the lab; he deserves the credit. We also thank all our collaborators worldwide: @JuliaPuchan, @ryangrui, @Jieun_Han1, @Yseeleuthner, @Drinchai, @zhangpeng1202, @KhorenPonsin, @Mchaldebas, @yifeng_evo, @ALNeehus….

10/ We thus add an additional piece to the puzzle of human immunity to M. tuberculosis with the study of inborn errors of immunity (affected molecules in red).

9/ In summary, human LY9 polarizes naïve CD4+ T cells toward memory TH1* cells by inducing T-bet and RORγT. LY9 costimulation enhances TCR-driven IFN-γ production of memory TH1*, but not TH1, cells in a T cell–intrinsic manner via NFAT1 and RORγT.

8/ Finally, LY9 costimulation drives NFAT1 and RORγT to enhance IFN-γ production in TH1* cells. The LY9-NFAT1-RORγT axis forms a positive feedback loop to enhance the activation of TCR-primed TH1* cells.

7/ We show that LY9 operates in a CD4+ αβ T cell–intrinsic manner to promote the expression of T-bet and RORγT, suggesting that LY9 promotes the differentiation of primed naive CD4+ αβ T lymphocytes into mature (IFN-γ–producing) TH1* cells.

6/ Specifically, inherited LY9 deficiency impairs IFN-γ production by Mycobacterium-specific CD4+ αβ T lymphocytes, which are CD4+ αβ memory T cells known to be enriched within the CCR4−CCR6+CXCR3+ TH1* compartment, the function of which depends on RORγT in humans.

5/ We showed that LY9 deficiency impairs the production of IFN-γ by TH1* cells in ways that are dependent on T cell receptors (TCR) and on Mycobacterium.

4/ LY9 (lymphocyte antigen 9) encodes LY9 (also known as SLAMF3 or CD229), a transmembrane glycoprotein, expressed exclusively in hematopoietic cells. LY9-deficient patients display no abnormalities in any of the lymphoid and myeloid leukocyte subsets by immunophenotyping.

3) The patients are homozygous for frameshift variants in LY9 (p.G61Vfs3* and p.H351Rfs*22), resulting in complete absence of LY9 surface expression across all their leukocytes.

2/ We report unrelated patients with tuberculosis, who are homozygous for predicted loss-of-function in LY9, corresponding to a high enrichment in our TB cohort as compared to controls: {adjusted odds ratio [OR; 95% confidence interval (CI)] = 81.7 [7.9 to 10,986.5], P = 0.00012}

1/ We are delighted to share our work published in @SciImmunolgyidentifying the role of LY9 in CD4+ T cell IFN-γ immunity to Mycobacterium tuberculosis.(.

RT @anne_puel: 1/ Excited to share our latest publication in @PNASNews! We report two patients with autosomal recessive RelB deficiency. Ch….

RT @ImmunoPodcast: A new @Nature paper from Drs. Andrés Arias (@AriasAAS) and Anna-Lena Neehus (@ALNeehu) explores how two cousins with a #….

RT @stutangye: @casanova_lab @austmus @eurekaprizes Thanks JL. Couldn’t have done it without you and your team and the many great projects….

RT @ImmunoSketch: Hidden within your immune system, TNF is the secret weapon that keeps tuberculosis at bay. @BoissonDupuis @Casanova_lab….

RT @InstitutImagine: Félicitations à @casanova_lab pour leur nouvel article dans @nature mettant en évidence la première déficience hérédit….