Elevated IgE from Attenuated CARD11 Signaling: Lessons from Atopic Mice and Humans

Overview

Journal Curr Opin Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2022 Nov 5

PMID 36334349

Authors

Joel L Pomerantz

Joshua D Milner

Andrew L Snow

Affiliations

Soon will be listed here.

Abstract

CARD11 encodes a large scaffold protein responsible for integrating antigen-receptor engagement with downstream signaling to NF-kB and other outputs in lymphocytes. Over the past 10 years, several human-inborn errors of immunity have been linked to pathogenic CARD11 mutations. Most recently, severe atopic patients were discovered that carried heterozygous dominant-negative CARD11 mutations. Here, we review the mechanistic connections between attenuated CARD11 signaling, elevated IgE, and atopy, comparing and contrasting key insights from both human patients and murine models. Continued investigation of abnormal CARD11 signaling in both contexts should inform novel therapeutic strategies to combat allergic pathogenesis.

Citing Articles

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References

Egawa T, Albrecht B, Favier B, Sunshine M, Mirchandani K, OBrien W . Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation. Curr Biol. 2003; 13(14):1252-8. DOI: 10.1016/s0960-9822(03)00491-3. View

Bedsaul J, Carter N, Deibel K, Hutcherson S, Jones T, Wang Z . Mechanisms of Regulated and Dysregulated CARD11 Signaling in Adaptive Immunity and Disease. Front Immunol. 2018; 9:2105. PMC: 6156143. DOI: 10.3389/fimmu.2018.02105. View

Lyons J, Milner J . Primary atopic disorders. J Exp Med. 2018; 215(4):1009-1022. PMC: 5881472. DOI: 10.1084/jem.20172306. View

Bedsaul J, Shah N, Hutcherson S, Pomerantz J . Mechanistic impact of oligomer poisoning by dominant-negative CARD11 variants. iScience. 2022; 25(2):103810. PMC: 8844825. DOI: 10.1016/j.isci.2022.103810. View

Liu Y, Wang Z, De La Torre R, Barling A, Tsujikawa T, Hornick N . Trim32 Deficiency Enhances Th2 Immunity and Predisposes to Features of Atopic Dermatitis. J Invest Dermatol. 2016; 137(2):359-366. PMC: 5258687. DOI: 10.1016/j.jid.2016.09.020. View

Shi J, Sun S . TCR signaling to NF-κB and mTORC1: Expanding roles of the CARMA1 complex. Mol Immunol. 2015; 68(2 Pt C):546-57. PMC: 4679546. DOI: 10.1016/j.molimm.2015.07.024. View

Meitlis I, Allenspach E, Bauman B, Phan I, Dabbah G, Schmitt E . Multiplexed Functional Assessment of Genetic Variants in CARD11. Am J Hum Genet. 2020; 107(6):1029-1043. PMC: 7820631. DOI: 10.1016/j.ajhg.2020.10.015. View

Sefer A, Abolhassani H, Ober F, Kayaoglu B, Bilgic Eltan S, Kara A . Expanding the Clinical and Immunological Phenotypes and Natural History of MALT1 Deficiency. J Clin Immunol. 2022; 42(3):634-652. DOI: 10.1007/s10875-021-01191-4. View

Yang Y, Yang C, Chan W, Wang Z, Deibel K, Pomerantz J . Molecular Determinants of Scaffold-induced Linear Ubiquitinylation of B Cell Lymphoma/Leukemia 10 (Bcl10) during T Cell Receptor and Oncogenic Caspase Recruitment Domain-containing Protein 11 (CARD11) Signaling. J Biol Chem. 2016; 291(50):25921-25936. PMC: 5207066. DOI: 10.1074/jbc.M116.754028. View

10.

Nakaya M, Xiao Y, Zhou X, Chang J, Chang M, Cheng X . Inflammatory T cell responses rely on amino acid transporter ASCT2 facilitation of glutamine uptake and mTORC1 kinase activation. Immunity. 2014; 40(5):692-705. PMC: 4074507. DOI: 10.1016/j.immuni.2014.04.007. View

11.

Dorjbal B, Stinson J, Ma C, Weinreich M, Miraghazadeh B, Hartberger J . Hypomorphic caspase activation and recruitment domain 11 (CARD11) mutations associated with diverse immunologic phenotypes with or without atopic disease. J Allergy Clin Immunol. 2018; 143(4):1482-1495. PMC: 6395549. DOI: 10.1016/j.jaci.2018.08.013. View

12.

Yang D, Conze D, Whitmarsh A, Barrett T, Davis R, Rincon M . Differentiation of CD4+ T cells to Th1 cells requires MAP kinase JNK2. Immunity. 1998; 9(4):575-85. DOI: 10.1016/s1074-7613(00)80640-8. View

13.

Hutcherson S, Bedsaul J, Pomerantz J . . J Immunol. 2021; 207(4):1150-1164. PMC: 8355193. DOI: 10.4049/jimmunol.2001233. View

14.

Li J, Ritelli M, Ma C, Rao G, Habib T, Corvilain E . Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β. Sci Immunol. 2019; 4(41). PMC: 7014825. DOI: 10.1126/sciimmunol.aax7965. View

15.

Hara H, Wada T, Bakal C, Kozieradzki I, Suzuki S, Suzuki N . The MAGUK family protein CARD11 is essential for lymphocyte activation. Immunity. 2003; 18(6):763-75. DOI: 10.1016/s1074-7613(03)00148-1. View

16.

Yin H, Karayel O, Chao Y, Seeholzer T, Hamp I, Plettenburg O . A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells. Cell Mol Life Sci. 2022; 79(2):112. PMC: 8803816. DOI: 10.1007/s00018-022-04154-z. View

17.

Gelman H, Dines J, Berg J, Berger A, Brnich S, Hisama F . Recommendations for the collection and use of multiplexed functional data for clinical variant interpretation. Genome Med. 2019; 11(1):85. PMC: 6925490. DOI: 10.1186/s13073-019-0698-7. View

18.

Lamason R, Kupfer A, Pomerantz J . The dynamic distribution of CARD11 at the immunological synapse is regulated by the inhibitory kinesin GAKIN. Mol Cell. 2010; 40(5):798-809. PMC: 3032410. DOI: 10.1016/j.molcel.2010.11.007. View

19.

Policheni A, Horikawa K, Milla L, Kofler J, Bouillet P, Belz G . CARD11 is dispensable for homeostatic responses and suppressive activity of peripherally induced FOXP3 regulatory T cells. Immunol Cell Biol. 2019; 97(8):740-752. DOI: 10.1111/imcb.12268. View

20.

Peled A, Sarig O, Sun G, Samuelov L, Ma C, Zhang Y . Loss-of-function mutations in caspase recruitment domain-containing protein 14 (CARD14) are associated with a severe variant of atopic dermatitis. J Allergy Clin Immunol. 2018; 143(1):173-181.e10. DOI: 10.1016/j.jaci.2018.09.002. View