Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis

Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis Publisher Pubmed

Olguin Calderon D ; Kilpatrick L E ; Conil C ; Philippot Q ; Ogishi M ; Vellutini J ; Han J E ; Keating N ; Li H ; Rao G ; Bohlen J ; Lay C S ; Platt S ; Kerner G Show All Authors

Olguin Calderon D
Kilpatrick L E
Conil C
Philippot Q
Ogishi M
Vellutini J
Han J E
Keating N
Li H
Rao G
Bohlen J
Lay C S
Platt S
Kerner G
Feredj E
Peel J N
Momenilandi M
Seeleuthner Y
Laine C
Soudee C
Leloup C
Debuisson C
Lanternier F
Bitoun S
Pavy S
Mariette X
Rafik A
Skhoun H
El Ouazzani H
Abderahmani Ghorfi I
El Baghdadi J
Baena A
Tejada Giraldo M
Barrera L F
Arias A A
Fabio G
Carrabba M
Emiroglu M
Bezrodnik L
El Zein L
Hammoud H
Gregersen P K
Terrier B
Leon Lopez R
Touzet M
Pestre V
Pasquet M
Rogge L
Fayon M
Galode F
Jeziorski E
Duffy D
Quintana Murci L
Patin E
Cunningham Rundles C
Meyts I
Zhang S Y
Zhang Q
Jouanguy E
Boisson B
Rosain J
Beziat V
Shahrooei M
Mahdaviani S A
Rezaei N
Parvaneh N
Chavoshzadeh Z
Yazdanpanah N
Aladjidi N
Noguera Julian A
Esteve Sole A
Alsina L
Mansouri D
Keles S
Ortakoylu M G
Aygun D
Yucel E
Kiykim A
Camcioglu Y
Ma C S
Tangye S G
Zhang P
Abel L
Craggs P D
Casanova J L
Cobat A
Puel A
Bustamante J
Hill S J
Boisson Dupuis S

Source: The Journal of experimental medicine Published:2026

Abstract

Homozygosity for rare loss-of-function IL23R variants abolishes IL-23-dependent IFN-γ production by lymphocytes, including NK and innate-like T cells, thereby underlying clinical disease due to weakly virulent mycobacterial species. We report selective enrichment in homozygosity for four hypomorphic IL23R variants in our cohort of patients with tuberculosis. Three of these IL23R alleles are rare (G300V, G149R, and L372F), with a minor allele frequency (MAF) under 1%, but the fourth (R381Q) is surprisingly common, with an MAF as high as 10.2% in certain populations. The other 15 missense alleles found in the homozygous state in public databases are isomorphic. The four hypomorphic IL-23R variants identified dimerize with IL-12Rβ1 and bind IL-23. However, their function is impaired by low levels of cell surface expression (R381Q, G300V) and/or as a consequence of conformational changes altering agonist efficacy. IFN-γ production in response to IL-23 is impaired in innate-like T cells and NK cells. These data suggest that recessive partial IL-23R deficiency, whether due to rare or common variants, confers a predisposition to tuberculosis while preserving immunity to less virulent mycobacteria. © 2026 Olguin Calderon et al.

Style	Citing Format
MLA	Olguin Calderon D, et al.. "Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis." The Journal of experimental medicine, vol. 223, no. 8, 2026, pp. -.
APA	Olguin Calderon D, Kilpatrick L E, Conil C, Philippot Q, Ogishi M, Vellutini J, Han J E, Keating N, Li H, Rao G, Bohlen J, Lay C S, Platt S, Kerner G, Feredj E, Peel J N, Momenilandi M, Seeleuthner Y, Laine C, ... Boisson Dupuis S (2026). Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis. The Journal of experimental medicine, 223(8), -.
Chicago	Olguin Calderon D, Kilpatrick L E, Conil C, Philippot Q, Ogishi M, Vellutini J, Han J E, et al.. "Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis." The Journal of experimental medicine 223, no. 8 (2026): -.
Harvard	Olguin Calderon D et al. (2026) 'Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis', The Journal of experimental medicine, 223(8), pp. -.
Vancouver	Olguin Calderon D, Kilpatrick L E, Conil C, Philippot Q, Ogishi M, Vellutini J, et al.. Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis. The Journal of experimental medicine. 2026;223(8):-.
BibTex	@article{ author = {Olguin Calderon D and Kilpatrick L E and Conil C and Philippot Q and Ogishi M and Vellutini J and Han J E and Keating N and Li H and Rao G and Bohlen J and Lay C S and Platt S and Kerner G and Feredj E and Peel J N and Momenilandi M and Seeleuthner Y and Laine C and Soudee C and Leloup C and Debuisson C and Lanternier F and Bitoun S and Pavy S and Mariette X and Rafik A and Skhoun H and El Ouazzani H and Abderahmani Ghorfi I and El Baghdadi J and Baena A and Tejada Giraldo M and Barrera L F and Arias A A and Fabio G and Carrabba M and Emiroglu M and Bezrodnik L and El Zein L and Hammoud H and Gregersen P K and Terrier B and Leon Lopez R and Touzet M and Pestre V and Pasquet M and Rogge L and Fayon M and Galode F and Jeziorski E and Duffy D and Quintana Murci L and Patin E and Cunningham Rundles C and Meyts I and Zhang S Y and Zhang Q and Jouanguy E and Boisson B and Rosain J and Beziat V and Shahrooei M and Mahdaviani S A and Rezaei N and Parvaneh N and Chavoshzadeh Z and Yazdanpanah N and Aladjidi N and Noguera Julian A and Esteve Sole A and Alsina L and Mansouri D and Keles S and Ortakoylu M G and Aygun D and Yucel E and Kiykim A and Camcioglu Y and Ma C S and Tangye S G and Zhang P and Abel L and Craggs P D and Casanova J L and Cobat A and Puel A and Bustamante J and Hill S J and Boisson Dupuis S}, title = {Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis}, journal = {The Journal of experimental medicine}, volume = {223}, number = {8}, pages = {-}, year = {2026} }
RIS	TY - JOUR AU - Olguin Calderon D AU - Kilpatrick L E AU - Conil C AU - Philippot Q AU - Ogishi M AU - Vellutini J AU - Han J E AU - Keating N AU - Li H AU - Rao G AU - Bohlen J AU - Lay C S AU - Platt S AU - Kerner G AU - Feredj E AU - Peel J N AU - Momenilandi M AU - Seeleuthner Y AU - Laine C AU - Soudee C AU - Leloup C AU - Debuisson C AU - Lanternier F AU - Bitoun S AU - Pavy S AU - Mariette X AU - Rafik A AU - Skhoun H AU - El Ouazzani H AU - Abderahmani Ghorfi I AU - El Baghdadi J AU - Baena A AU - Tejada Giraldo M AU - Barrera L F AU - Arias A A AU - Fabio G AU - Carrabba M AU - Emiroglu M AU - Bezrodnik L AU - El Zein L AU - Hammoud H AU - Gregersen P K AU - Terrier B AU - Leon Lopez R AU - Touzet M AU - Pestre V AU - Pasquet M AU - Rogge L AU - Fayon M AU - Galode F AU - Jeziorski E AU - Duffy D AU - Quintana Murci L AU - Patin E AU - Cunningham Rundles C AU - Meyts I AU - Zhang S Y AU - Zhang Q AU - Jouanguy E AU - Boisson B AU - Rosain J AU - Beziat V AU - Shahrooei M AU - Mahdaviani S A AU - Rezaei N AU - Parvaneh N AU - Chavoshzadeh Z AU - Yazdanpanah N AU - Aladjidi N AU - Noguera Julian A AU - Esteve Sole A AU - Alsina L AU - Mansouri D AU - Keles S AU - Ortakoylu M G AU - Aygun D AU - Yucel E AU - Kiykim A AU - Camcioglu Y AU - Ma C S AU - Tangye S G AU - Zhang P AU - Abel L AU - Craggs P D AU - Casanova J L AU - Cobat A AU - Puel A AU - Bustamante J AU - Hill S J AU - Boisson Dupuis S TI - Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis JO - The Journal of experimental medicine VL - 223 IS - 8 SP - EP - PY - 2026 ER -

Style

Citing Format

MLA

Olguin Calderon D, et al.. "Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis." The Journal of experimental medicine, vol. 223, no. 8, 2026, pp. -.

APA

Olguin Calderon D, Kilpatrick L E, Conil C, Philippot Q, Ogishi M, Vellutini J, Han J E, Keating N, Li H, Rao G, Bohlen J, Lay C S, Platt S, Kerner G, Feredj E, Peel J N, Momenilandi M, Seeleuthner Y, Laine C, ... Boisson Dupuis S (2026). Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis. The Journal of experimental medicine, 223(8), -.

Chicago

Olguin Calderon D, Kilpatrick L E, Conil C, Philippot Q, Ogishi M, Vellutini J, Han J E, et al.. "Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis." The Journal of experimental medicine 223, no. 8 (2026): -.

Harvard

Olguin Calderon D et al. (2026) 'Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis', The Journal of experimental medicine, 223(8), pp. -.

Vancouver

Olguin Calderon D, Kilpatrick L E, Conil C, Philippot Q, Ogishi M, Vellutini J, et al.. Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis. The Journal of experimental medicine. 2026;223(8):-.

BibTex

@article{ author = {Olguin Calderon D and Kilpatrick L E and Conil C and Philippot Q and Ogishi M and Vellutini J and Han J E and Keating N and Li H and Rao G and Bohlen J and Lay C S and Platt S and Kerner G and Feredj E and Peel J N and Momenilandi M and Seeleuthner Y and Laine C and Soudee C and Leloup C and Debuisson C and Lanternier F and Bitoun S and Pavy S and Mariette X and Rafik A and Skhoun H and El Ouazzani H and Abderahmani Ghorfi I and El Baghdadi J and Baena A and Tejada Giraldo M and Barrera L F and Arias A A and Fabio G and Carrabba M and Emiroglu M and Bezrodnik L and El Zein L and Hammoud H and Gregersen P K and Terrier B and Leon Lopez R and Touzet M and Pestre V and Pasquet M and Rogge L and Fayon M and Galode F and Jeziorski E and Duffy D and Quintana Murci L and Patin E and Cunningham Rundles C and Meyts I and Zhang S Y and Zhang Q and Jouanguy E and Boisson B and Rosain J and Beziat V and Shahrooei M and Mahdaviani S A and Rezaei N and Parvaneh N and Chavoshzadeh Z and Yazdanpanah N and Aladjidi N and Noguera Julian A and Esteve Sole A and Alsina L and Mansouri D and Keles S and Ortakoylu M G and Aygun D and Yucel E and Kiykim A and Camcioglu Y and Ma C S and Tangye S G and Zhang P and Abel L and Craggs P D and Casanova J L and Cobat A and Puel A and Bustamante J and Hill S J and Boisson Dupuis S}, title = {Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis}, journal = {The Journal of experimental medicine}, volume = {223}, number = {8}, pages = {-}, year = {2026} }

RIS

TY - JOUR
AU - Olguin Calderon D
AU - Kilpatrick L E
AU - Conil C
AU - Philippot Q
AU - Ogishi M
AU - Vellutini J
AU - Han J E
AU - Keating N
AU - Li H
AU - Rao G
AU - Bohlen J
AU - Lay C S
AU - Platt S
AU - Kerner G
AU - Feredj E
AU - Peel J N
AU - Momenilandi M
AU - Seeleuthner Y
AU - Laine C
AU - Soudee C
AU - Leloup C
AU - Debuisson C
AU - Lanternier F
AU - Bitoun S
AU - Pavy S
AU - Mariette X
AU - Rafik A
AU - Skhoun H
AU - El Ouazzani H
AU - Abderahmani Ghorfi I
AU - El Baghdadi J
AU - Baena A
AU - Tejada Giraldo M
AU - Barrera L F
AU - Arias A A
AU - Fabio G
AU - Carrabba M
AU - Emiroglu M
AU - Bezrodnik L
AU - El Zein L
AU - Hammoud H
AU - Gregersen P K
AU - Terrier B
AU - Leon Lopez R
AU - Touzet M
AU - Pestre V
AU - Pasquet M
AU - Rogge L
AU - Fayon M
AU - Galode F
AU - Jeziorski E
AU - Duffy D
AU - Quintana Murci L
AU - Patin E
AU - Cunningham Rundles C
AU - Meyts I
AU - Zhang S Y
AU - Zhang Q
AU - Jouanguy E
AU - Boisson B
AU - Rosain J
AU - Beziat V
AU - Shahrooei M
AU - Mahdaviani S A
AU - Rezaei N
AU - Parvaneh N
AU - Chavoshzadeh Z
AU - Yazdanpanah N
AU - Aladjidi N
AU - Noguera Julian A
AU - Esteve Sole A
AU - Alsina L
AU - Mansouri D
AU - Keles S
AU - Ortakoylu M G
AU - Aygun D
AU - Yucel E
AU - Kiykim A
AU - Camcioglu Y
AU - Ma C S
AU - Tangye S G
AU - Zhang P
AU - Abel L
AU - Craggs P D
AU - Casanova J L
AU - Cobat A
AU - Puel A
AU - Bustamante J
AU - Hill S J
AU - Boisson Dupuis S
TI - Humans Homozygous for Rare or Common Hypomorphic Il23r Variants Are Prone to Tuberculosis
JO - The Journal of experimental medicine
VL - 223
IS - 8
SP -
EP -
PY - 2026
ER -

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