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• W1907842654 abstract "Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These 3 CARD-BCL10-MALT1 (CBM) complexes activate nuclear factor κB in both the innate and adaptive arms of immunity. Human inherited defects of the 3 components of the CBM complex, including the 2 adaptors CARD9 and CARD11 and the 2 core components BCL10 and MALT1, have recently been reported. Biallelic loss-of-function mutant alleles underlie several different immunologic and clinical phenotypes, which can be assigned to 2 distinct categories. Isolated invasive fungal infections of unclear cellular basis are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1, and BCL10 deficiencies. Interestingly, human subjects with these mutations have some features in common with the corresponding knockout mice, but other features are different between human subjects and mice. Moreover, germline and somatic gain-of-function mutations of MALT1, BCL10, and CARD11 have also been found in patients with other lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including loss-of-function and gain-of-function mutations, highlights the contribution of each of the components of the CBM complex to human immunity. Discuss this article on the JACI Journal Club blog: www.jaci-online.blogspot.com. The CBM complex is a cytosolic heterotrimer formed by a caspase recruitment domain (CARD) protein, B-cell lymphoma 10 (BCL10), and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). Three CARD family adaptor molecules have been shown to form CBM complexes: CARD9, CARD10 (also known as CARD-containing MAGUK protein 3 [CARMA3]), and CARD11 (also known as CARMA1). Human CARD9 is a 536-amino-acid adaptor protein. It possesses an N-terminal CARD domain (mediating homophilic interactions between CARD-containing molecules) and a C-terminal coiled-coil region that serves as an oligomerization domain. CARD10 is a 1032-amino-acid protein that binds to BCL10-MALT1.1Thome M. Multifunctional roles for MALT1 in T-cell activation.Nat Rev Immunol. 2008; 8: 495-500Crossref PubMed Scopus (101) Google Scholar CARD11 is 1154 amino acids long and belongs to both the membrane-associated guanylate kinase (MAGUK)2Caruana G. Genetic studies define MAGUK proteins as regulators of epithelial cell polarity.Int J Dev Biol. 2002; 46: 511-518PubMed Google Scholar and CARD families. MALT1 is an 824-amino-acid caspase-like cysteine protease that contains a CARD domain, 2 immunoglobulin-like domains, and a C-terminal caspase-like domain. Finally, BCL10 is a 233-amino-acid intracellular signaling protein characterized by an amino-terminal CARD motif and a Ser/Thr-rich carboxyl terminus of unknown function.3Thome M. CARMA1, BCL-10 and MALT1 in lymphocyte development and activation.Nat Rev Immunol. 2004; 4: 348-359Crossref PubMed Scopus (332) Google Scholar, 4Thome M. Charton J.E. Pelzer C. Hailfinger S. Antigen receptor signaling to NF-kappaB via CARMA1, BCL10, and MALT1.Cold Spring Harb Perspect Biol. 2010; 2: a003004Crossref Scopus (185) Google Scholar The 2 immunoglobulin-like domains of MALT1 bind to BCL10 through a motif composed of a short stretch of amino acids located just after the CARD of BCL10. CARD motifs of BCL10 and MALT1 allow binding to the 3 CARD proteins forming the heterotrimer. In human subjects and mice the CBM complex mediates nuclear factor κB (NF-κB) and mitogen-activated protein kinase activation in a cell type–specific and nonredundant manner after stimulation of various immune receptors, as described below. The NF-κB transcription factor plays a critical role in innate and adaptive immune regulation, cell memory, cell survival/apoptosis, and cell-cycle progression. Different cell types contain different members of the CARD family: CARD9 in myeloid cells,5Hara H. Saito T. CARD9 versus CARMA1 in innate and adaptive immunity.Trends Immunol. 2009; 30: 234-242Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar CARD10 in epithelial cells,6Jiang T. Grabiner B. Zhu Y. Jiang C. Li H. You Y. et al.CARMA3 is crucial for EGFR-Induced activation of NF-kappaB and tumor progression.Cancer Res. 2011; 71: 2183-2192Crossref PubMed Scopus (74) Google Scholar, 7McAllister-Lucas L.M. Jin X. Gu S. Siu K. McDonnell S. Ruland J. et al.The CARMA3-Bcl10-MALT1 signalosome promotes angiotensin II-dependent vascular inflammation and atherogenesis.J Biol Chem. 2010; 285: 25880-25884Crossref PubMed Scopus (55) Google Scholar, 8McAllister-Lucas L.M. Ruland J. Siu K. Jin X. Gu S. Kim D.S. et al.CARMA3/Bcl10/MALT1-dependent NF-kappaB activation mediates angiotensin II-responsive inflammatory signaling in nonimmune cells.Proc Natl Acad Sci U S A. 2007; 104: 139-144Crossref PubMed Scopus (141) Google Scholar and CARD11 in lymphocytes5Hara H. Saito T. CARD9 versus CARMA1 in innate and adaptive immunity.Trends Immunol. 2009; 30: 234-242Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar (Fig 1). In lymphocytes the CBM complex acts downstream of the T-cell receptor (TCR) or B-cell receptor (BCR), controlling lymphocyte activation and adaptive immunity.9Hara H. Wada T. Bakal C. Kozieradzki I. Suzuki S. Suzuki N. et al.The MAGUK family protein CARD11 is essential for lymphocyte activation.Immunity. 2003; 18: 763-775Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar, 10Ruland J. Duncan G.S. Elia A. del Barco Barrantes I. Nguyen L. Plyte S. et al.Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure.Cell. 2001; 104: 33-42Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 11Ruland J. Duncan G.S. Wakeham A. Mak T.W. Differential requirement for Malt1 in T and B cell antigen receptor signaling.Immunity. 2003; 19: 749-758Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar, 12Wang D. You Y. Case S.M. McAllister-Lucas L.M. Wang L. DiStefano P.S. et al.A requirement for CARMA1 in TCR-induced NF-kappa B activation.Nat Immunol. 2002; 3: 830-835Crossref PubMed Scopus (252) Google Scholar It has also been implicated in B-cell activating factor receptor and Toll-like receptor (TLR) 4 signaling in B cells13Fischer K.D. Tedford K. Wirth T. New roles for Bcl10 in B-cell development and LPS response.Trends Immunol. 2004; 25: 113-116Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 14Yu M. Chen Y. He Y. Podd A. Fu G. Wright J.A. et al.Critical role of B cell lymphoma 10 in BAFF-regulated NF-kappaB activation and survival of anergic B cells.J Immunol. 2012; 189: 5185-5193Crossref PubMed Scopus (15) Google Scholar and in the signaling of several natural killer (NK) receptors, such as NK1.1, Ly49H, NKG2D, and Ly49D.15Gross O. Grupp C. Steinberg C. Zimmermann S. Strasser D. Hannesschlager N. et al.Multiple ITAM-coupled NK-cell receptors engage the Bcl10/Malt1 complex via Carma1 for NF-kappaB and MAPK activation to selectively control cytokine production.Blood. 2008; 112: 2421-2428Crossref PubMed Scopus (75) Google Scholar, 16Malarkannan S. Regunathan J. Chu H. Kutlesa S. Chen Y. Zeng H. et al.Bcl10 plays a divergent role in NK cell-mediated cytotoxicity and cytokine generation.J Immunol. 2007; 179: 3752-3762Crossref PubMed Scopus (35) Google Scholar In myeloid cells the CBM complex is involved in innate immune responses, in which it acts downstream from C-type lectin receptors, such as Dectin-1, Dectin-2, or Mincle,17Bhattacharyya S. Xue L. Devkota S. Chang E. Morris S. Tobacman J.K. Carrageenan-induced colonic inflammation is reduced in Bcl10 null mice and increased in IL-10-deficient mice.Mediators Inflamm. 2013; 2013: 397642Crossref PubMed Scopus (42) Google Scholar, 18Dong W. Liu Y. Peng J. Chen L. Zou T. Xiao H. et al.The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4.J Biol Chem. 2006; 281: 26029-26040Crossref PubMed Scopus (77) Google Scholar, 19Goodridge H.S. Shimada T. Wolf A.J. Hsu Y.M. Becker C.A. Lin X. et al.Differential use of CARD9 by dectin-1 in macrophages and dendritic cells.J Immunol. 2009; 182: 1146-1154Crossref PubMed Scopus (156) Google Scholar, 20Gringhuis S.I. Wevers B.A. Kaptein T.M. van Capel T.M. Theelen B. Boekhout T. et al.Selective C-Rel activation via Malt1 controls anti-fungal T(H)-17 immunity by dectin-1 and dectin-2.PLoS Pathog. 2011; 7: e1001259Crossref PubMed Scopus (132) Google Scholar, 21Marion S. Mazzolini J. Herit F. Bourdoncle P. Kambou-Pene N. Hailfinger S. et al.The NF-kappaB signaling protein Bcl10 regulates actin dynamics by controlling AP1 and OCRL-bearing vesicles.Dev Cell. 2012; 23: 954-967Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 22Strasser D. Neumann K. Bergmann H. Marakalala M.J. Guler R. Rojowska A. et al.Syk kinase-coupled C-type lectin receptors engage protein kinase C-sigma to elicit Card9 adaptor-mediated innate immunity.Immunity. 2012; 36: 32-42Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar, 23Tada R. Ikeda F. Aoki K. Yoshikawa M. Kato Y. Adachi Y. et al.Barley-derived beta-D-glucan induces immunostimulation via a dectin-1-mediated pathway.Immunol Lett. 2009; 123: 144-148Crossref PubMed Scopus (58) Google Scholar, 24Xu S. Huo J. Lee K.G. Kurosaki T. Lam K.P. Phospholipase Cgamma2 is critical for Dectin-1-mediated Ca2+ flux and cytokine production in dendritic cells.J Biol Chem. 2009; 284: 7038-7046Crossref PubMed Scopus (120) Google Scholar or other receptors, such as FcγR and TLRs. Finally, the CBM complex is involved in signaling downstream of TLR417Bhattacharyya S. Xue L. Devkota S. Chang E. Morris S. Tobacman J.K. Carrageenan-induced colonic inflammation is reduced in Bcl10 null mice and increased in IL-10-deficient mice.Mediators Inflamm. 2013; 2013: 397642Crossref PubMed Scopus (42) Google Scholar, 25Bhattacharyya S. Dudeja P.K. Tobacman J.K. Lipopolysaccharide activates NF-kappaB by TLR4-Bcl10-dependent and independent pathways in colonic epithelial cells.Am J Physiol Gastrointest Liver Physiol. 2008; 295: G784-G790Crossref PubMed Scopus (30) Google Scholar, 26Bhattacharyya S. Dudeja P.K. Tobacman J.K. Tumor necrosis factor alpha-induced inflammation is increased but apoptosis is inhibited by common food additive carrageenan.J Biol Chem. 2010; 285: 39511-39522Crossref PubMed Scopus (34) Google Scholar and G protein–coupled receptor signaling in epithelial cells (Fig 1).27LeibundGut-Landmann S. Gross O. Robinson M.J. Osorio F. Slack E.C. Tsoni S.V. et al.Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17.Nat Immunol. 2007; 8: 630-638Crossref PubMed Scopus (930) Google Scholar, 28Wegener E. Krappmann D. CARD-Bcl10-Malt1 signalosomes: missing link to NF-kappaB.Sci STKE. 2007; 2007: pe21Crossref PubMed Scopus (64) Google Scholar We describe here the broad spectrum of clinical and immunologic features of the primary immunodeficiencies caused by inborn errors of 4 of the 5 individual members of the human CBM complex. Studies of these primary immunodeficiencies should improve our understanding of the specific role of each of these components in immunity. The first patients with autosomal recessive (AR) MALT1 deficiency to be reported were 2 siblings from a consanguineous Lebanese family (P1 and P2).29Jabara H.H. Ohsumi T. Chou J. Massaad M.J. Benson H. Megarbane A. et al.A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency.J Allergy Clin Immunol. 2013; 132: 151-158Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar Both had experienced recurrent pulmonary infections since the age of 4 months, resulting in bronchiectasis. Both also had mastoiditis, chronic aphthous ulcers, cheilitis, gingivitis, esophagitis, gastritis, and duodenitis. Despite a history of vaccination with tetanus and unconjugated pneumococcal polysaccharide vaccines, anti-tetanus antibody and antibodies to all pneumococcal serotypes titers were nonprotective in both patients. P1 also had meningitis (caused by Streptococcus pneumoniae and Haemophilus influenzae). Biopsy of the small intestine showed villous atrophy in P1 and abnormally large numbers of intraepithelial lymphocytes in P2. Candida albicans was cultured from the duodenal biopsy sample and stools of P2. Cytomegalovirus was repeatedly recovered in the urine of both patients. Both patients had growth retardation but normal neurologic development. Despite intravenous immunoglobulin replacement therapy, both died from respiratory failure, P1 at 13.5 years of age and P2 at 7 years of age. A third patient (P3) was subsequently described by McKinnon et al.30McKinnon M.L. Rozmus J. Fung S.Y. Hirschfeld A.F. Del Bel K.L. Thomas L. et al.Combined immunodeficiency associated with homozygous MALT1 mutations.J Allergy Clin Immunol. 2014; 133 (e1-7): 1458-1462Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar This patient, a 15-year-old girl with consanguineous parents of Kurdish descent, presented with growth retardation, an eczema-like rash since age 2 weeks, and persistent severe dermatitis, skin infections with Staphylococcus aureus, varicella-zoster virus, and herpes simplex virus 1. P3 also had severe inflammatory gastrointestinal disease and multiple episodes of pneumonia, chronic inflammatory lung disease, bronchiectasis, clubbing, and chronic granulation tissue. Very recently, a fourth patient (P4) has been reported. This patient, a male infant with nonconsanguineous parents, had generalized rash, intestinal inflammation, and severe infections, including cytomegalovirus pneumonitis.31Punwani D. Wang H. Chan A.Y. Cowan M.J. Mallott J. Sunderam U. et al.Combined immunodeficiency due to MALT1 mutations, treated by hematopoietic cell transplantation.J Clin Immunol. 2015; 35: 135-146Crossref PubMed Scopus (74) Google Scholar P1 and P2 were homozygous for a missense mutation (S89I) located in the CARD domain of MALT1. The mutation had no effect on MALT1 mRNA levels, but no protein was detectable in the lysates of PHA T-cell blasts. P1 and P2 had normal numbers of CD3+CD4+, CD3+CD8+, and CD19+ cells and normal serum immunoglobulin levels. An analysis of naive and memory T cells was performed once on CD4+ cells from P1, and the percentages were within normal ranges (68% CD4+CD45RA+ cells and 38% CD4+CD45RO+ cells). B-cell subsets were not examined.29Jabara H.H. Ohsumi T. Chou J. Massaad M.J. Benson H. Megarbane A. et al.A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency.J Allergy Clin Immunol. 2013; 132: 151-158Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar P3 was homozygous for a missense mutation (W580S). This residue is part of an α-helical linker region, and the aromatic group of W580 interacts with hydrophobic residues of the caspase-like domain. The mutation resulted in normal MALT1 mRNA levels but very low protein levels. Lymphocyte numbers were within the normal range. The proportion of CD31+ T cells was high, with skewing toward the CD4+ T helper subset. CD4+CD25+CD127+lo forkhead box protein 3–positive regulatory T-cell numbers were normal. However, P3 had very low B-cell counts, with developmental arrest characterized by high percentages of naive B cells and an almost complete absence of marginal zone B cells and low levels of switched memory B cells. Serum immunoglobulin levels were normal.30McKinnon M.L. Rozmus J. Fung S.Y. Hirschfeld A.F. Del Bel K.L. Thomas L. et al.Combined immunodeficiency associated with homozygous MALT1 mutations.J Allergy Clin Immunol. 2014; 133 (e1-7): 1458-1462Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar P4 was a compound heterozygote with 2 nonsynonymous variants affecting MALT1 exon 10, a splice acceptor defect (cDNA c.1019-2A>G), and a single nucleotide deletion, leading to a frameshift within the paracaspase domain and truncation after 18 missense codons (Y353fs*18). No protein was detectable in the lysates of PBMCs. P4 showed expansion of CD4+ and CD8+ T-cell populations, with high proportions of naive CD45RA+ T cells. B and NK cells were present, but immunoglobulin levels were low (Fig 1 and Table I).29Jabara H.H. Ohsumi T. Chou J. Massaad M.J. Benson H. Megarbane A. et al.A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency.J Allergy Clin Immunol. 2013; 132: 151-158Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar, 30McKinnon M.L. Rozmus J. Fung S.Y. Hirschfeld A.F. Del Bel K.L. Thomas L. et al.Combined immunodeficiency associated with homozygous MALT1 mutations.J Allergy Clin Immunol. 2014; 133 (e1-7): 1458-1462Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 31Punwani D. Wang H. Chan A.Y. Cowan M.J. Mallott J. Sunderam U. et al.Combined immunodeficiency due to MALT1 mutations, treated by hematopoietic cell transplantation.J Clin Immunol. 2015; 35: 135-146Crossref PubMed Scopus (74) Google Scholar, 32Torres J.M. Martinez-Barricarte R. García-Gómez S. Mazariegos M.S. Itan Y. Boisson B. et al.Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity.J Clin Invest. 2014; 124: 5239-5248Crossref PubMed Scopus (83) Google Scholar, 33Greil J. Rausch T. Giese T. Bandapalli O.R. Daniel V. Bekeredjian-Ding I. et al.Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency.J Allergy Clin Immunol. 2013; 131: 1376-1383.e3Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar, 34Stepensky P. Keller B. Buchta M. Kienzler A.K. Elpeleg O. Somech R. et al.Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects.J Allergy Clin Immunol. 2013; 131: 477-485.e1Abstract Full Text Full Text PDF PubMed Scopus (137) Google ScholarTable ISummary of the 3 human CMB complex deficiencies associated with CIDsClinical diagnosisLymphocyte phenotypePatientsMutationConsanguinityCellular responseMALT1CID29Jabara H.H. Ohsumi T. Chou J. Massaad M.J. Benson H. Megarbane A. et al.A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency.J Allergy Clin Immunol. 2013; 132: 151-158Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar•Normal total numbers of T and B cellsSiblings P1 and P2 (both deceased)•Homozygous•Loss of protein expression; c.266G>T S89IParents were first cousins•Impaired proliferative response of PBMCs to mitogens PHA, ConA, PWM, and anti-CD3 and antigens (tetanus toxoid, diphtheria toxin, and Candida species)•Impaired IκB-α degradation and IL-2 production on TCR stimulationCID30McKinnon M.L. Rozmus J. Fung S.Y. Hirschfeld A.F. Del Bel K.L. Thomas L. et al.Combined immunodeficiency associated with homozygous MALT1 mutations.J Allergy Clin Immunol. 2014; 133 (e1-7): 1458-1462Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar•Severe B-cell lymphopenia; developmental arrest: small numbers of transitional B cells, increased percentages of naive B cells, almost no marginal zone and low levels of switched memory B cellsP3•Homozygous•Very low levels of protein expression; W580SParents were first cousins•Absence of IκB-α degradation and p65 phosphorylation in primary T cells after PMA/ionomycin stimulation•Paracaspase activity affected•Absence of T-cell proliferation and blast formation after PHA stimulation and abolition of IL-2 secretionCID31Punwani D. Wang H. Chan A.Y. Cowan M.J. Mallott J. Sunderam U. et al.Combined immunodeficiency due to MALT1 mutations, treated by hematopoietic cell transplantation.J Clin Immunol. 2015; 35: 135-146Crossref PubMed Scopus (74) Google Scholar•Expansion of CD4+ and CD8+ T-cell populations with high proportions of naive CD45RA+ T cells•B and NK cells were present, but immunoglobulin levels were low.P4•Compound heterozygote mutations•Loss of protein expression•Splice acceptor defect, cDNA c.1019-2A>G, and a single nucleotide deletion (Y353fs*18)Nonconsanguineous parents•PBMCs: Impaired proliferative responses to PHA and ConA and inability to phosphorylate NF-κB or degrade IκB•Reduced levels of IL-2 and IFN-γ after activation with PMA/ionomycin or anti-CD3/CD28 in T cellsBCL10CID32Torres J.M. Martinez-Barricarte R. García-Gómez S. Mazariegos M.S. Itan Y. Boisson B. et al.Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity.J Clin Invest. 2014; 124: 5239-5248Crossref PubMed Scopus (83) Google Scholar•Normal total numbers of T and B cells but mostly with a naive phenotypeP5 (deceased)•Homozygous•Loss of protein expression, g.85741978C>T; IVS1+1G>AParents were first cousins•Normal responses to TLR1/2, TLR4, TLR2/6, and Dectin-1 signaling by MDMs and MDDCs•Impaired TLR4, TLR2/6, and Dectin-1 signaling in fibroblasts•Blocked T-cell proliferation in response to TCR stimulationCARD11CID33Greil J. Rausch T. Giese T. Bandapalli O.R. Daniel V. Bekeredjian-Ding I. et al.Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency.J Allergy Clin Immunol. 2013; 131: 1376-1383.e3Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar•Normal T- and B-cell numbers•Predominantly naive phenotype of CD4+ and CD8+ T cells•Peripheral blood B cells, mostly naive, with a transitional B-cell phenotype•Absence of regulatory T cellsP6•Homozygous•Protein detected, Q945XParents were first cousins•Impaired T-cell proliferation after PBMC stimulation with T-cell mitogens (PHA, ConA, or anti-CD3 mAb)•Strongly impaired proinflammatory cytokine production after LPS stimulation and weak production after PMA/ionomycin stimulation•Disturbed TCR-mediated T-cell functionCID34Stepensky P. Keller B. Buchta M. Kienzler A.K. Elpeleg O. Somech R. et al.Deficiency of caspase recruitment domain family, member 11 (CARD11), causes profound combined immunodeficiency in human subjects.J Allergy Clin Immunol. 2013; 131: 477-485.e1Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar•Normal CD4 and CD8 T-cell counts but with a predominantly naive phenotype, very low levels of regulatory T cells, effector memory cells, and terminally differentiated effector cells•B cells are mostly naive and transitionalP7•Homozygous1377-bp genomic deletion encompassing the entire sequence of exon 21•No protein expressionParents were first cousins•No IκB-α degradation or p65 phosphorylation after anti-IgM and PMA stimulation•No induction of intracellular adhesion molecule 1 and CD25 in B cells after BCR stimulation•Low percentages of IL-2, IL-17, and IFN-γ in CD4 T cells after PMA/ionomycin stimulation•Impaired upregulation of OX40, CD25, and ICOS expression in response to TCR/CD28 stimulation•Abolished proliferation of T cells in response to CD3/CD28 stimulationCID, Combined immunodeficiency; ICOS, inducible costimulator; MDDC, monocyte-derived dendritic cell; MDM, monocyte-derived macrophage. Open table in a new tab CID, Combined immunodeficiency; ICOS, inducible costimulator; MDDC, monocyte-derived dendritic cell; MDM, monocyte-derived macrophage. PBMCs from P1 and P2 displayed impaired proliferative responses to mitogens (PHA, concanavalin A [ConA], and lectin from Phytolacca americana [pokeweed {PWM}], and anti-CD3), or antigens (tetanus toxoid, diphtheria toxin, and Candida species). Their T cells (PHA T-cell blasts) did not degrade IκB-α or produce IL-2 after stimulation with phorbol 12-myristate 13-acetate (PMA) plus ionomycin (PMA/ionomycin).29Jabara H.H. Ohsumi T. Chou J. Massaad M.J. Benson H. Megarbane A. et al.A homozygous mucosa-associated lymphoid tissue 1 (MALT1) mutation in a family with combined immunodeficiency.J Allergy Clin Immunol. 2013; 132: 151-158Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar Similarly, no IκB-α degradation or p65 phosphorylation was observed in primary T cells from P3 after PMA/ionomycin stimulation. The roles of MALT1 in PBMCs from P3 were investigated by testing the effect of the mutation on paracaspase activity and the scaffold function central to CBM complex formation. MALT1 paracaspase activity was studied by assessing the cleavage of its substrate, BCL10, and was found to be absent in P3.30McKinnon M.L. Rozmus J. Fung S.Y. Hirschfeld A.F. Del Bel K.L. Thomas L. et al.Combined immunodeficiency associated with homozygous MALT1 mutations.J Allergy Clin Immunol. 2014; 133 (e1-7): 1458-1462Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 35Turvey S.E. Durandy A. Fischer A. Fung S.Y. Geha R.S. Gewies A. et al.The CARD11-BCL10-MALT1 (CBM) signalosome complex: stepping into the limelight of human primary immunodeficiency.J Allergy Clin Immunol. 2014; 134: 276-284Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar PBMCs from P4 displayed impaired proliferative responses to PHA and ConA. Moreover, these cells were unable to phosphorylate NF-κB or degrade IκB. After activation with PMA/ionomycin or anti-CD3/CD28, P4's T cells had reduced levels of IL-2 and IFN-γ.31Punwani D. Wang H. Chan A.Y. Cowan M.J. Mallott J. Sunderam U. et al.Combined immunodeficiency due to MALT1 mutations, treated by hematopoietic cell transplantation.J Clin Immunol. 2015; 35: 135-146Crossref PubMed Scopus (74) Google Scholar Like the patients, Malt1-deficient mice had normal numbers of peripheral T cells with a normal subset distribution but a defective proliferative response to mitogens or anti-CD3 antibody. The number of follicular B cells in the spleens of Malt1−/− mice was normal, but there were very few marginal zone B cells and peritoneal B1 cells, the cells responsible for producing antibodies against type II T-independent antigens. B-cell activating factor receptor signaling was impaired in the mutant mice, and immunoglobulin levels were low, which was at odds with the findings for the human deficiency. As in humans, Malt1 was found essential for T-cell activation, proliferation, and IL-2 production in response to TCR ligation. It was also found required for the NF-κB activation induced by the TCR, but not for TNF-α or IL-1 signaling (Table II).9Hara H. Wada T. Bakal C. Kozieradzki I. Suzuki S. Suzuki N. et al.The MAGUK family protein CARD11 is essential for lymphocyte activation.Immunity. 2003; 18: 763-775Abstract Full Text Full Text PDF PubMed Scopus (279) Google Scholar, 10Ruland J. Duncan G.S. Elia A. del Barco Barrantes I. Nguyen L. Plyte S. et al.Bcl10 is a positive regulator of antigen receptor-induced activation of NF-kappaB and neural tube closure.Cell. 2001; 104: 33-42Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 11Ruland J. Duncan G.S. Wakeham A. Mak T.W. Differential requirement for Malt1 in T and B cell antigen receptor signaling.Immunity. 2003; 19: 749-758Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar, 13Fischer K.D. Tedford K. Wirth T. New roles for Bcl10 in B-cell development and LPS response.Trends Immunol. 2004; 25: 113-116Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 15Gross O. Grupp C. Steinberg C. Zimmermann S. Strasser D. Hannesschlager N. et al.Multiple ITAM-coupled NK-cell receptors engage the Bcl10/Malt1 complex via Carma1 for NF-kappaB and MAPK activation to selectively control cytokine production.Blood. 2008; 112: 2421-2428Crossref PubMed Scopus (75) Google Scholar, 21Marion S. Mazzolini J. Herit F. Bourdoncle P. Kambou-Pene N. Hailfinger S. et al.The NF-kappaB signaling protein Bcl10 regulates actin dynamics by controlling AP1 and OCRL-bearing vesicles.Dev Cell. 2012; 23: 954-967Abstract Full Text Full Text PDF PubMed Scopus (63) Google Scholar, 23Tada R. Ikeda F. Aoki K. Yoshikawa M. Kato Y. Adachi Y. et al.Barley-derived beta-D-glucan induces immunostimulation via a dectin-1-mediated pathway.Immunol Lett. 2009; 123: 144-148Crossref PubMed Scopus (58) Google Scholar, 27LeibundGut-Landmann S. Gross O. Robinson M.J. Osorio F. Slack E.C. Tsoni S.V. et al.Syk- and CARD9-dependent coupling" @default.
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• W1907842654 date "2015-11-01" @default.
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• W1907842654 title "Genetic errors of the human caspase recruitment domain–B-cell lymphoma 10–mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity" @default.
• W1907842654 cites W1533493044 @default.
• W1907842654 cites W1563487810 @default.
• W1907842654 cites W1964412713 @default.
• W1907842654 cites W1964435410 @default.
• W1907842654 cites W1964465182 @default.
• W1907842654 cites W1969202402 @default.
• W1907842654 cites W1969950015 @default.
• W1907842654 cites W1972698666 @default.
• W1907842654 cites W1973227469 @default.
• W1907842654 cites W1974366841 @default.
• W1907842654 cites W1976672229 @default.
• W1907842654 cites W1977642281 @default.
• W1907842654 cites W1979201919 @default.
• W1907842654 cites W1987374413 @default.
• W1907842654 cites W1988387964 @default.
• W1907842654 cites W1996305237 @default.
• W1907842654 cites W1996388035 @default.
• W1907842654 cites W2003131704 @default.
• W1907842654 cites W2004980094 @default.
• W1907842654 cites W2005329318 @default.
• W1907842654 cites W2006338784 @default.
• W1907842654 cites W2007576081 @default.
• W1907842654 cites W2013277175 @default.
• W1907842654 cites W2013417742 @default.
• W1907842654 cites W2014293477 @default.
• W1907842654 cites W2018705412 @default.
• W1907842654 cites W2024767191 @default.
• W1907842654 cites W2029295983 @default.
• W1907842654 cites W2029663467 @default.
• W1907842654 cites W2031855605 @default.
• W1907842654 cites W2033732585 @default.
• W1907842654 cites W2039253450 @default.
• W1907842654 cites W2045179022 @default.
• W1907842654 cites W2046392894 @default.
• W1907842654 cites W2047320677 @default.
• W1907842654 cites W2058488029 @default.
• W1907842654 cites W2065666266 @default.
• W1907842654 cites W2069236772 @default.
• W1907842654 cites W2073900277 @default.
• W1907842654 cites W2074362469 @default.
• W1907842654 cites W2075626786 @default.
• W1907842654 cites W2076364657 @default.
• W1907842654 cites W2080986462 @default.
• W1907842654 cites W2081246083 @default.
• W1907842654 cites W2083391898 @default.
• W1907842654 cites W2085732250 @default.
• W1907842654 cites W2088852852 @default.
• W1907842654 cites W2089623844 @default.
• W1907842654 cites W2091759234 @default.
• W1907842654 cites W2092807701 @default.
• W1907842654 cites W2096308522 @default.
• W1907842654 cites W2096977835 @default.
• W1907842654 cites W2099136629 @default.
• W1907842654 cites W2099823946 @default.
• W1907842654 cites W2105275733 @default.
• W1907842654 cites W2108010371 @default.
• W1907842654 cites W2111211555 @default.
• W1907842654 cites W2120368369 @default.
• W1907842654 cites W2124977947 @default.
• W1907842654 cites W2133971099 @default.
• W1907842654 cites W2139372097 @default.
• W1907842654 cites W2139792086 @default.
• W1907842654 cites W2144165833 @default.
• W1907842654 cites W2145463019 @default.
• W1907842654 cites W2146099217 @default.
• W1907842654 cites W2154542711 @default.
• W1907842654 cites W2158102062 @default.
• W1907842654 cites W2161059598 @default.
• W1907842654 cites W2161880998 @default.
• W1907842654 cites W2164500783 @default.
• W1907842654 cites W2164970623 @default.
• W1907842654 cites W2170191276 @default.
• W1907842654 cites W2170852908 @default.
• W1907842654 cites W2327298320 @default.
• W1907842654 doi "https://doi.org/10.1016/j.jaci.2015.06.031" @default.
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