Human inherited CCR2 deficiency underlies progressive polycystic lung disease

Anna Lena Neehus; Brenna Carey; Marija Landekic; Patricia Panikulam; Gail Deutsch; Masato Ogishi; Carlos A. Arango-Franco; Quentin Philippot; Mohammadreza Modaresi; Iraj Mohammadzadeh; Melissa Corcini Berndt; Darawan Rinchai; Tom Le Voyer; Jérémie Rosain; Mana Momenilandi; Marta Martin-Fernandez; Taushif Khan; Jonathan Bohlen; Ji Eun Han; Alexandre Deslys; Mathilde Bernard; Tania Gajardo-Carrasco; Camille Soudée; Corentin Le Floc'h; Mélanie Migaud; Yoann Seeleuthner; Mi Sun Jang; Eirini Nikolouli; Simin Seyedpour; Hugues Begueret; Jean François Emile; Pierre Le Guen; Guido Tavazzi; Costanza Natalia Julia Colombo; Federico Capra Marzani; Micol Angelini; Francesca Trespidi; Stefano Ghirardello; Nasrin Alipour; Anne Molitor; Raphael Carapito; Mohsen Mazloomrezaei; Hassan Rokni-Zadeh; Majid Changi-Ashtiani; Chantal Brouzes; Pablo Vargas; Alessandro Borghesi; Nico Lachmann; Seiamak Bahram; Bruno Crestani; Susanta Pahari; Larry S. Schlesinger; Nico Marr; Dusan Bugonovic; Stéphanie Boisson-Dupuis; Vivien Béziat; Laurent Abel; Raphael Borie; Lisa R. Young; Robin Deterding; Mohammad Shahrooei; Nima Rezaei; Nima Parvaneh; Daniel Craven; Philippe Gros; Danielle Malo; Fernando E. Sepulveda; Lawrence M. Nogee; Nathalie Aladjidi; Bruce C. Trapnell; Jean Laurent Casanova; Jacinta Bustamante

doi:10.1016/j.cell.2023.11.036

Human inherited CCR2 deficiency underlies progressive polycystic lung disease

Anna Lena Neehus, Brenna Carey, Marija Landekic, Patricia Panikulam, Gail Deutsch, Masato Ogishi, Carlos A. Arango-Franco, Quentin Philippot, Mohammadreza Modaresi, Iraj Mohammadzadeh, Melissa Corcini Berndt, Darawan Rinchai, Tom Le Voyer, Jérémie Rosain, Mana Momenilandi, Marta Martin-Fernandez, Taushif Khan, Jonathan Bohlen, Ji Eun Han, Alexandre DeslysMathilde Bernard, Tania Gajardo-Carrasco, Camille Soudée, Corentin Le Floc'h, Mélanie Migaud, Yoann Seeleuthner, Mi Sun Jang, Eirini Nikolouli, Simin Seyedpour, Hugues Begueret, Jean François Emile, Pierre Le Guen, Guido Tavazzi, Costanza Natalia Julia Colombo, Federico Capra Marzani, Micol Angelini, Francesca Trespidi, Stefano Ghirardello, Nasrin Alipour, Anne Molitor, Raphael Carapito, Mohsen Mazloomrezaei, Hassan Rokni-Zadeh, Majid Changi-Ashtiani, Chantal Brouzes, Pablo Vargas, Alessandro Borghesi, Nico Lachmann, Seiamak Bahram, Bruno Crestani, Susanta Pahari, Larry S. Schlesinger, Nico Marr, Dusan Bugonovic, Stéphanie Boisson-Dupuis, Vivien Béziat, Laurent Abel, Raphael Borie, Lisa R. Young, Robin Deterding, Mohammad Shahrooei, Nima Rezaei, Nima Parvaneh, Daniel Craven, Philippe Gros, Danielle Malo, Fernando E. Sepulveda, Lawrence M. Nogee, Nathalie Aladjidi, Bruce C. Trapnell, Jean Laurent Casanova, Jacinta Bustamante

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca²⁺ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

Original language	English (US)
Pages (from-to)	390-408.e23
Journal	Cell
Volume	187
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2023.11.036
State	Published - Jan 18 2024

Keywords

PAP
chemotaxis
cystic lung disease
macrophage
monocyte
recurrent infection

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2023.11.036

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Neehus, A. L., Carey, B., Landekic, M., Panikulam, P., Deutsch, G., Ogishi, M., Arango-Franco, C. A., Philippot, Q., Modaresi, M., Mohammadzadeh, I., Corcini Berndt, M., Rinchai, D., Le Voyer, T., Rosain, J., Momenilandi, M., Martin-Fernandez, M., Khan, T., Bohlen, J., Han, J. E., ... Bustamante, J. (2024). Human inherited CCR2 deficiency underlies progressive polycystic lung disease. Cell, 187(2), 390-408.e23. https://doi.org/10.1016/j.cell.2023.11.036

Neehus, AL, Carey, B, Landekic, M, Panikulam, P, Deutsch, G, Ogishi, M, Arango-Franco, CA, Philippot, Q, Modaresi, M, Mohammadzadeh, I, Corcini Berndt, M, Rinchai, D, Le Voyer, T, Rosain, J, Momenilandi, M, Martin-Fernandez, M, Khan, T, Bohlen, J, Han, JE, Deslys, A, Bernard, M, Gajardo-Carrasco, T, Soudée, C, Le Floc'h, C, Migaud, M, Seeleuthner, Y, Jang, MS, Nikolouli, E, Seyedpour, S, Begueret, H, Emile, JF, Le Guen, P, Tavazzi, G, Colombo, CNJ, Marzani, FC, Angelini, M, Trespidi, F, Ghirardello, S, Alipour, N, Molitor, A, Carapito, R, Mazloomrezaei, M, Rokni-Zadeh, H, Changi-Ashtiani, M, Brouzes, C, Vargas, P, Borghesi, A, Lachmann, N, Bahram, S, Crestani, B, Pahari, S, Schlesinger, LS, Marr, N, Bugonovic, D, Boisson-Dupuis, S, Béziat, V, Abel, L, Borie, R, Young, LR, Deterding, R, Shahrooei, M, Rezaei, N, Parvaneh, N, Craven, D, Gros, P, Malo, D, Sepulveda, FE, Nogee, LM, Aladjidi, N, Trapnell, BC, Casanova, JL & Bustamante, J 2024, 'Human inherited CCR2 deficiency underlies progressive polycystic lung disease', Cell, vol. 187, no. 2, pp. 390-408.e23. https://doi.org/10.1016/j.cell.2023.11.036

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abstract = "We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Gu{\'e}rin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.",

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author = "Neehus, {Anna Lena} and Brenna Carey and Marija Landekic and Patricia Panikulam and Gail Deutsch and Masato Ogishi and Arango-Franco, {Carlos A.} and Quentin Philippot and Mohammadreza Modaresi and Iraj Mohammadzadeh and {Corcini Berndt}, Melissa and Darawan Rinchai and {Le Voyer}, Tom and J{\'e}r{\'e}mie Rosain and Mana Momenilandi and Marta Martin-Fernandez and Taushif Khan and Jonathan Bohlen and Han, {Ji Eun} and Alexandre Deslys and Mathilde Bernard and Tania Gajardo-Carrasco and Camille Soud{\'e}e and {Le Floc'h}, Corentin and M{\'e}lanie Migaud and Yoann Seeleuthner and Jang, {Mi Sun} and Eirini Nikolouli and Simin Seyedpour and Hugues Begueret and Emile, {Jean Fran{\c c}ois} and {Le Guen}, Pierre and Guido Tavazzi and Colombo, {Costanza Natalia Julia} and Marzani, {Federico Capra} and Micol Angelini and Francesca Trespidi and Stefano Ghirardello and Nasrin Alipour and Anne Molitor and Raphael Carapito and Mohsen Mazloomrezaei and Hassan Rokni-Zadeh and Majid Changi-Ashtiani and Chantal Brouzes and Pablo Vargas and Alessandro Borghesi and Nico Lachmann and Seiamak Bahram and Bruno Crestani and Susanta Pahari and Schlesinger, {Larry S.} and Nico Marr and Dusan Bugonovic and St{\'e}phanie Boisson-Dupuis and Vivien B{\'e}ziat and Laurent Abel and Raphael Borie and Young, {Lisa R.} and Robin Deterding and Mohammad Shahrooei and Nima Rezaei and Nima Parvaneh and Daniel Craven and Philippe Gros and Danielle Malo and Sepulveda, {Fernando E.} and Nogee, {Lawrence M.} and Nathalie Aladjidi and Trapnell, {Bruce C.} and Casanova, {Jean Laurent} and Jacinta Bustamante",

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month = jan,

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doi = "10.1016/j.cell.2023.11.036",

language = "English (US)",

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T1 - Human inherited CCR2 deficiency underlies progressive polycystic lung disease

AU - Neehus, Anna Lena

AU - Carey, Brenna

AU - Landekic, Marija

AU - Panikulam, Patricia

AU - Deutsch, Gail

AU - Ogishi, Masato

AU - Arango-Franco, Carlos A.

AU - Philippot, Quentin

AU - Modaresi, Mohammadreza

AU - Mohammadzadeh, Iraj

AU - Corcini Berndt, Melissa

AU - Rinchai, Darawan

AU - Le Voyer, Tom

AU - Rosain, Jérémie

AU - Momenilandi, Mana

AU - Martin-Fernandez, Marta

AU - Khan, Taushif

AU - Bohlen, Jonathan

AU - Han, Ji Eun

AU - Deslys, Alexandre

AU - Bernard, Mathilde

AU - Gajardo-Carrasco, Tania

AU - Soudée, Camille

AU - Le Floc'h, Corentin

AU - Migaud, Mélanie

AU - Seeleuthner, Yoann

AU - Jang, Mi Sun

AU - Nikolouli, Eirini

AU - Seyedpour, Simin

AU - Begueret, Hugues

AU - Emile, Jean François

AU - Le Guen, Pierre

AU - Tavazzi, Guido

AU - Colombo, Costanza Natalia Julia

AU - Marzani, Federico Capra

AU - Angelini, Micol

AU - Trespidi, Francesca

AU - Ghirardello, Stefano

AU - Alipour, Nasrin

AU - Molitor, Anne

AU - Carapito, Raphael

AU - Mazloomrezaei, Mohsen

AU - Rokni-Zadeh, Hassan

AU - Changi-Ashtiani, Majid

AU - Brouzes, Chantal

AU - Vargas, Pablo

AU - Borghesi, Alessandro

AU - Lachmann, Nico

AU - Bahram, Seiamak

AU - Crestani, Bruno

AU - Pahari, Susanta

AU - Schlesinger, Larry S.

AU - Marr, Nico

AU - Bugonovic, Dusan

AU - Boisson-Dupuis, Stéphanie

AU - Béziat, Vivien

AU - Abel, Laurent

AU - Borie, Raphael

AU - Young, Lisa R.

AU - Deterding, Robin

AU - Shahrooei, Mohammad

AU - Rezaei, Nima

AU - Parvaneh, Nima

AU - Craven, Daniel

AU - Gros, Philippe

AU - Malo, Danielle

AU - Sepulveda, Fernando E.

AU - Nogee, Lawrence M.

AU - Aladjidi, Nathalie

AU - Trapnell, Bruce C.

AU - Casanova, Jean Laurent

AU - Bustamante, Jacinta

PY - 2024/1/18

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N2 - We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

AB - We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

KW - PAP

KW - chemotaxis

KW - cystic lung disease

KW - macrophage

KW - monocyte

KW - recurrent infection

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DO - 10.1016/j.cell.2023.11.036

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VL - 187

SP - 390-408.e23

JO - Cell

JF - Cell

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ER -

Human inherited CCR2 deficiency underlies progressive polycystic lung disease

Abstract

Keywords

ASJC Scopus subject areas

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