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Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells.

Publication ,  Journal Article
Kolev, M; West, EE; Kunz, N; Chauss, D; Moseman, EA; Rahman, J; Freiwald, T; Balmer, ML; Lötscher, J; Dimeloe, S; Rosser, EC; Wedderburn, LR ...
Published in: Immunity
March 17, 2020

Intrinsic complement C3 activity is integral to human T helper type 1 (Th1) and cytotoxic T cell responses. Increased or decreased intracellular C3 results in autoimmunity and infections, respectively. The mechanisms regulating intracellular C3 expression remain undefined. We identified complement, including C3, as among the most significantly enriched biological pathway in tissue-occupying cells. We generated C3-reporter mice and confirmed that C3 expression was a defining feature of tissue-immune cells, including T cells and monocytes, occurred during transendothelial diapedesis, and depended on integrin lymphocyte-function-associated antigen 1 (LFA-1) signals. Immune cells from patients with leukocyte adhesion deficiency type 1 (LAD-1) had reduced C3 transcripts and diminished effector activities, which could be rescued proportionally by intracellular C3 provision. Conversely, increased C3 expression by T cells from arthritis patients correlated with disease severity. Our study defines integrins as key controllers of intracellular complement, demonstrates that perturbations in the LFA-1-C3-axis contribute to primary immunodeficiency, and identifies intracellular C3 as biomarker of severity in autoimmunity.

Duke Scholars

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Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

March 17, 2020

Volume

52

Issue

3

Start / End Page

513 / 527.e8

Location

United States

Related Subject Headings

  • Transendothelial and Transepithelial Migration
  • Signal Transduction
  • Monocytes
  • Middle Aged
  • Mice, Inbred C57BL
  • Male
  • Lymphocytes
  • Lymphocyte Function-Associated Antigen-1
  • Integrins
  • Immunology
 

Citation

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Kolev, M., West, E. E., Kunz, N., Chauss, D., Moseman, E. A., Rahman, J., … Kemper, C. (2020). Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells. Immunity, 52(3), 513-527.e8. https://doi.org/10.1016/j.immuni.2020.02.006
Kolev, Martin, Erin E. West, Natalia Kunz, Daniel Chauss, E Ashley Moseman, Jubayer Rahman, Tilo Freiwald, et al. “Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells.Immunity 52, no. 3 (March 17, 2020): 513-527.e8. https://doi.org/10.1016/j.immuni.2020.02.006.
Kolev M, West EE, Kunz N, Chauss D, Moseman EA, Rahman J, et al. Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells. Immunity. 2020 Mar 17;52(3):513-527.e8.
Kolev, Martin, et al. “Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells.Immunity, vol. 52, no. 3, Mar. 2020, pp. 513-527.e8. Pubmed, doi:10.1016/j.immuni.2020.02.006.
Kolev M, West EE, Kunz N, Chauss D, Moseman EA, Rahman J, Freiwald T, Balmer ML, Lötscher J, Dimeloe S, Rosser EC, Wedderburn LR, Mayer-Barber KD, Bohrer A, Lavender P, Cope A, Wang L, Kaplan MJ, Moutsopoulos NM, McGavern D, Holland SM, Hess C, Kazemian M, Afzali B, Kemper C. Diapedesis-Induced Integrin Signaling via LFA-1 Facilitates Tissue Immunity by Inducing Intrinsic Complement C3 Expression in Immune Cells. Immunity. 2020 Mar 17;52(3):513-527.e8.
Journal cover image

Published In

Immunity

DOI

EISSN

1097-4180

Publication Date

March 17, 2020

Volume

52

Issue

3

Start / End Page

513 / 527.e8

Location

United States

Related Subject Headings

  • Transendothelial and Transepithelial Migration
  • Signal Transduction
  • Monocytes
  • Middle Aged
  • Mice, Inbred C57BL
  • Male
  • Lymphocytes
  • Lymphocyte Function-Associated Antigen-1
  • Integrins
  • Immunology