A Rare Association Between Leukocyte Adhesion Deficiency Type I and Psoriasis in Humans

El-Sayed, Zeinab; El‐Ghoneimy, Dalia; Abdallah, Heba M. I.; Afifi, Hanaa M.

doi:10.4168/aair.2011.3.2.138

Cited by 10 publications

(9 citation statements)

References 10 publications

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“…This deficiency manifests in recurrent skin infections without pus formation, persistent gingivitis, periodontitis, and psoriasis. This patient showed persistent neutrophilia, reduced CD18 expression on CD4 ϩ T cells (which normally express ␣ L ␤ 2 and ␣ M ␤ 2 but not ␣ X ␤ 2 ), and normal expression of CD18 and CD11c on PMN (70). These observations suggest the importance of ␣ M ␤ 2 but not of ␣ X ␤ 2 in the resolution of inflammation and for the inhibition of autoimmune diseases such as psoriasis associated with defective M egress.…”

Section: Discussionmentioning

confidence: 69%

“…Particularly, low levels of CD18 (␤ 2 ) expression on leukocytes have been implicated in the pathogenesis of psoriasis and different granulomas (69). A patient with a rare variant of LAD-1 with defective CD11b expression, but normal CD18 expression, was described recently (70). This deficiency manifests in recurrent skin infections without pus formation, persistent gingivitis, periodontitis, and psoriasis.…”

Section: Discussionmentioning

confidence: 99%

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Distinct Effects of Integrins α_Xβ₂and α_Mβ₂on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses

et al. 2017

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Integrins ␣ M ␤ 2 and ␣ X ␤ 2 are homologous adhesive receptors that are expressed on many of the same leukocyte populations and bind many of the same ligands. Although ␣ M ␤ 2 was extensively characterized and implicated in leukocyte inflammatory and immune functions, the roles of ␣ X ␤ 2 remain largely obscure. Here, we tested the ability of mice deficient in integrin ␣ M ␤ 2 or ␣ X ␤ 2 to deal with opportunistic infections and the capacity of cells derived from these animals to execute inflammatory functions. The absence of ␣ M ␤ 2 affected the recruitment of polymorphonuclear neutrophils (PMN) to bacterial and fungal pathogens as well as to model inflammatory stimuli, and ␣ M ␤ 2 -deficient PMN displayed defective inflammatory functions. In contrast, deficiency of ␣ X ␤ 2 abrogated intraperitoneal recruitment and adhesive functions of monocytes and macrophages (M) and the ability of these cells to kill/phagocytose Candida albicans or Escherichia coli cells both ex vivo and in vivo. During systemic candidiasis, the absence of ␣ X ␤ 2 resulted in the loss of antifungal activity by tissue M and inhibited the production of tumor necrosis factor alpha (TNF-␣)/interleukin-6 (IL-6) in infected kidneys. Deficiency of ␣ M ␤ 2 suppressed M egress from the peritoneal cavity, decreased the production of anti-inflammatory IL-10, and stimulated the secretion of IL-6. The absence of ␣ X ␤ 2 , but not of ␣ M ␤ 2 , increased survival against a septic challenge with lipopolysaccharide (LPS) by 2-fold. Together, these results suggest that ␣ M ␤ 2 plays a primary role in PMN inflammatory functions and regulates the anti-inflammatory functions of M, whereas ␣ X ␤ 2 is central in the regulation of inflammatory functions of recruited and tissue-resident M.KEYWORDS Candida albicans, Escherichia coli, animal models, cytokines, infection control, inflammation, integrins, macrophages, monocytes, neutrophils I ntegrins are a large family of heterodimeric adhesive cell receptors that mediate a wide spectrum of cell-cell and cell-extracellular matrix (ECM) interactions (1). They are present on cell surfaces in a conformation in which they exhibit a relatively low affinity for their cognate ligands but become activated by environmental agonists to elicit their biological functions. The ␤ 2 integrin subfamily, expressed primarily by leukocytes, is composed of four members, which share a ␤ 2 (CD18) subunit. This subunit associates noncovalently with one of four distinct but structurally homologous ␣ subunits to form ␣ M ␤ 2 (CD11b/CD18, Mac-1, or CR3), ␣ X ␤ 2 , (CD11c/CD18, p150,95, or CR4), ␣ L ␤ 2 (CD11a/ CD18 or LFA-1), and ␣ D ␤ 2 (CD11d/CD18) (for reviews, see references 2 and 3). One of the most extensively characterized ␤ 2 integrins is ␣ M ␤ 2 , which is expressed on polymorphonuclear neutrophils (PMN), monocytes, macrophages (M), some subsets of cytotoxic T lymphocytes, and NK cells and has been implicated in the diverse responses of these cells, including chemotaxis, inflammation, phagocytosis, and cell-mediated killing ...

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Distinct Effects of Integrins α_Xβ₂and α_Mβ₂on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses

et al. 2017

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“…Importantly, unlike human psoriasis, IMQ-induced murine dermatitis does not progress to a chronic stage. According to our data presented in this study and previous reports, reduced CD18 expression levels are found on blood leukocytes in psoriasis patients (35)(36)(37)(38)(39), and in a recent independent study, an inflammatory CLA + Vg9Vd2 T cell subset in human blood capable of infiltrating the skin has been identified in psoriasis patients (25). To enhance these in part rather correlative data, we provide direct evidence for a causal relationship between reduced CD18 expression levels on immune cells and expansion of inflammatory skin-tropic gd T cells potentiating psoriasiform dermatitis in the chronic CD18 hypo PL/J psoriasis mouse model that closely mimics human psoriasis.…”

Section: Discussionmentioning

confidence: 80%

“…+ ab and gdTCR low gd T cells with a memory phenotype predominate in the skin infiltrate in CD18 hypo PL/J psoriasiform dermatitis Because normally, CD18 is highly expressed on ab and gd T cells and expression of CD18, ICAM-1, or ICAM-2 is altered in certain psoriasis patients (35)(36)(37)(38)(39), we set out to analyze the impact of reduced CD18 levels on gd T cell function and inflammatory cytokine and marker expression in psoriasiform dermatitis using the CD18 hypo PL/J mouse model. To characterize the skin infiltrate of affected CD18…”

Section: Cd4mentioning

confidence: 99%

“…Notably, reduced or altered expression of CD18 itself or of the b 2 integrin ligands ICAM-1 and -2, located in proximity to PSORS6 on 19p13 and PSORS2 on 17q25, respectively, may also affect susceptibility to psoriasis in humans, underlining the clinical relevance of the CD18 hypo PL/J psoriasis model (33)(34)(35)(36)(37)(38)(39). A critical role of CD4 + T cells in psoriasiform dermatitis of CD18 hypo PL/J mice was previously confirmed by resolution of skin disease after treatment anti-CD4 Abs (31).…”

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confidence: 99%

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Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Gatzka

Hainzl

Peters

et al. 2013

The Journal of Immunology

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IL-17 is a critical factor in the pathogenesis of psoriasis and other inflammatory diseases. The impact of γδ T cells, accounting for an important source of IL-17 in acute murine IL-23– and imiquimod-induced skin inflammation, in human psoriasis is still unclear. Using the polygenic CD18hypo PL/J psoriasis mouse model spontaneously developing chronic psoriasiform dermatitis due to reduced CD18/β2 integrin expression to 2–16% of wild-type levels, we investigated in this study the influence of adhesion molecule expression on generation of inflammatory γδ T cells and analyzed the occurrence of IL-17–producing γδ and CD4+ T cells at different disease stages. Severity of CD18hypo PL/J psoriasiform dermatitis correlated with a loss of skin-resident Vγ5+ T cells and concurrent skin infiltration with IL-17+, IL-22+, and TNF-α+ γδTCRlow cells preceded by increases in Vγ4+ T cells in local lymph nodes. In vitro, reduced CD18 levels promoted expansion of inflammatory memory-type γδ T cells in response to IL-7. Similar to IL-17 or IL-23/p19 depletion, injection of diseased CD18hypo PL/J mice with anti-γδTCR Abs significantly reduced skin inflammation and largely eliminated pathological γδ and CD4+ T cells. Moreover, CD18hypo γδ T cells induced allogeneic CD4+ T cell responses more potently than CD18wt counterparts and, upon adoptive transfer, triggered psoriasiform dermatitis in susceptible hosts. These results demonstrate a novel function of reduced CD18 levels in generation of pathological γδ T cells that was confirmed by detection of increases in CD18low γδ T cells in psoriasis patients and may also have implications for other inflammatory diseases.

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Variable CD18 expression in a 22‐year‐old female with leukocyte adhesion deficiency I: Clinical case and literature review

Bondarenko,

Boyarchuk,

Sakovich

et al. 2023

Clinical Case Reports

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Key Clinical MessagePartial leukocyte adhesion deficiency type 1 (LAD‐1) deficiency is extremely rare condition with milder infectious manifestation and immune system imbalance leads to increased risks of autoinflammatory complications, such as pyoderma gangrenosum, that can be triggered by trauma or pregnancy. In patients with spice‐site ITGB2 variants, partial expression can occur due to different β2 integrin isophorms expression.AbstractLAD‐1, OMIM ID #116920 is a rare, autosomal recessive disorder that results from mutations in the ITGB2 gene that encodes the CD18 β2 integrin subunit. According to the CD18 expression, LAD‐1 is categorized as severe (<2%), moderate (2%–30%), or mild (>30%). Here, we describe a 22‐year‐old female, who presented with inflammatory skin disease and oral cavity, as well as respiratory tract infections during the first year of life. LAD‐1 was diagnosed at the age of 2 years by low expression of CD18 (1%). Whole‐exome sequencing identified homozygous c. 59‐10C>A variant in the ITGB2 gene. Despite severe phenotype, the patient survived to adulthood without hematopoietic stem cell transplantation and became pregnant at the age of 20 years, with pregnancy complicated by a pyoderma gangrenosum‐like lesion. During her life, CD18 expression increased from 1% to 9%; at 22 years of age, 5% of neutrophils and 9% of lymphocytes were CD18+. All CD18+‐lymphocytes were predominantly memory/effector cytotoxic T cells. However, revertant mosaicism was not being established suggesting that CD18 expression variability may be mediated by other mechanisms such as different β2 integrin isophorms expression.

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A Rare Association Between Leukocyte Adhesion Deficiency Type I and Psoriasis in Humans

Cited by 10 publications

References 10 publications

Distinct Effects of Integrins α_Xβ₂and α_Mβ₂on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses

Distinct Effects of Integrins α_Xβ₂and α_Mβ₂on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Variable CD18 expression in a 22‐year‐old female with leukocyte adhesion deficiency I: Clinical case and literature review

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A Rare Association Between Leukocyte Adhesion Deficiency Type I and Psoriasis in Humans

Cited by 10 publications

References 10 publications

Distinct Effects of Integrins αXβ2and αMβ2on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses

Distinct Effects of Integrins αXβ2and αMβ2on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Variable CD18 expression in a 22‐year‐old female with leukocyte adhesion deficiency I: Clinical case and literature review

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Distinct Effects of Integrins α_Xβ₂and α_Mβ₂on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses

Distinct Effects of Integrins α_Xβ₂and α_Mβ₂on Leukocyte Subpopulations during Inflammation and Antimicrobial Responses