PMID- 32603507
OWN - NLM
STAT- MEDLINE
DCOM- 20210301
LR  - 20240331
IS  - 1531-4995 (Electronic)
IS  - 0023-852X (Print)
IS  - 0023-852X (Linking)
VI  - 131
IP  - 3
DP  - 2021 Mar
TI  - The Proximal Airway Is a Reservoir for Adaptive Immunologic Memory in Idiopathic 
      Subglottic Stenosis.
PG  - 610-617
LID - 10.1002/lary.28840 [doi]
AB  - OBJECTIVES/HYPOTHESIS: Characterization of the localized adaptive immune response 
      in the airway scar of patients with idiopathic subglottic stenosis (iSGS). STUDY 
      DESIGN: Basic Science. METHODS: Utilizing 36 patients with subglottic stenosis 
      (25 idiopathic subglottic stenosis [iSGS], 10 iatrogenic post-intubation stenosis 
      [iLTS], and one granulomatosis with polyangiitis [GPA]) we applied 
      immunohistochemical and immunologic techniques coupled with RNA sequencing. 
      RESULTS: iSGS, iLTS, and GPA demonstrate a significant immune infiltrate in the 
      subglottic scar consisting of adaptive cell subsets (T cells along with dendritic 
      cells). Interrogation of T cell subtypes showed significantly more CD69(+) 
      CD103(+) CD8(+) tissue resident memory T cells (T(RM) ) in the iSGS airway scar 
      than iLTS specimens (iSGS vs. iLTS; 50% vs. 28%, P = .0065). Additionally, 
      subglottic CD8(+) clones possessed T-cell receptor (TCR) sequences with known 
      antigen specificity for viral and intracellular pathogens. CONCLUSIONS: The human 
      subglottis is significantly enriched for CD8(+) tissue resident memory T cells in 
      iSGS, which possess TCR sequences proven to recognize viral and intracellular 
      pathogens. These results inform our understanding of iSGS, provide a direction 
      for future discovery, and demonstrate immunologic function in the human proximal 
      airway. Laryngoscope, 131:610-617, 2021.
CI  - (c) 2020 The American Laryngological, Rhinological and Otological Society, Inc.
FAU - Gelbard, Alexander
AU  - Gelbard A
AUID- ORCID: 0000-0003-0078-1305
AD  - Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical 
      Center, Nashville, Tennessee, U.S.A.
FAU - Wanjalla, Celestine
AU  - Wanjalla C
AD  - Department of Medicine, Division of Infectious Disease, Vanderbilt University 
      Medical Center, Nashville, Tennessee, U.S.A.
FAU - Wootten, Christopher T
AU  - Wootten CT
AD  - Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical 
      Center, Nashville, Tennessee, U.S.A.
FAU - Drake, Wonder P
AU  - Drake WP
AD  - Department of Medicine, Division of Infectious Disease, Vanderbilt University 
      Medical Center, Nashville, Tennessee, U.S.A.
FAU - Lowery, Anne S
AU  - Lowery AS
AD  - Department of Otolaryngology-Head & Neck Surgery, Vanderbilt University Medical 
      Center, Nashville, Tennessee, U.S.A.
FAU - Wheeler, David A
AU  - Wheeler DA
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      Texas, U.S.A.
FAU - Cardenas, Maria F
AU  - Cardenas MF
AD  - Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 
      Texas, U.S.A.
FAU - Sikora, Andrew G
AU  - Sikora AG
AD  - Bobby R. Alford Department of Otolaryngology-Head & Neck Surgery, Baylor College 
      of Medicine, Houston, Texas, U.S.A.
FAU - Pathak, Ravi R
AU  - Pathak RR
AD  - Bobby R. Alford Department of Otolaryngology-Head & Neck Surgery, Baylor College 
      of Medicine, Houston, Texas, U.S.A.
FAU - McDonnell, Wyatt
AU  - McDonnell W
AD  - 10x Genomics Inc, Pleasanton, California, U.S.A.
FAU - Mallal, Simon
AU  - Mallal S
AD  - Department of Medicine, Division of Infectious Disease, Vanderbilt University 
      Medical Center, Nashville, Tennessee, U.S.A.
FAU - Pilkinton, Mark
AU  - Pilkinton M
AD  - Department of Medicine, Division of Infectious Disease, Vanderbilt University 
      Medical Center, Nashville, Tennessee, U.S.A.
LA  - eng
GR  - P30 AI110527/AI/NIAID NIH HHS/United States
GR  - R01 HL146401/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20200630
PL  - United States
TA  - Laryngoscope
JT  - The Laryngoscope
JID - 8607378
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, T-Lymphocyte)
RN  - 0 (CD69 antigen)
RN  - 0 (CD8 Antigens)
RN  - 0 (Integrin alpha Chains)
RN  - 0 (Lectins, C-Type)
RN  - 0 (alpha E integrins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Airway Obstruction/*immunology
MH  - Antigens, CD/immunology
MH  - Antigens, Differentiation, T-Lymphocyte/immunology
MH  - CD8 Antigens/immunology
MH  - Cicatrix/*immunology
MH  - Constriction, Pathologic
MH  - Female
MH  - Glottis/immunology/pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - Immunologic Memory/*immunology
MH  - Integrin alpha Chains/immunology
MH  - Laryngostenosis/*immunology
MH  - Lectins, C-Type/immunology
MH  - Male
MH  - Middle Aged
MH  - T-Lymphocyte Subsets/*immunology
PMC - PMC7951501
MID - NIHMS1674572
OTO - NOTNLM
OT  - T cell receptor
OT  - TCR sequencing
OT  - clonotype
OT  - iSGS
OT  - resident memory
OT  - subglottis
COIS- Competing Interests: WJM is an employee and shareholder of 10x Genomics, Inc.
EDAT- 2020/07/01 06:00
MHDA- 2021/03/02 06:00
PMCR- 2022/03/01
CRDT- 2020/07/01 06:00
PHST- 2020/04/14 00:00 [received]
PHST- 2020/05/18 00:00 [revised]
PHST- 2020/05/21 00:00 [accepted]
PHST- 2020/07/01 06:00 [pubmed]
PHST- 2021/03/02 06:00 [medline]
PHST- 2020/07/01 06:00 [entrez]
PHST- 2022/03/01 00:00 [pmc-release]
AID - 10.1002/lary.28840 [doi]
PST - ppublish
SO  - Laryngoscope. 2021 Mar;131(3):610-617. doi: 10.1002/lary.28840. Epub 2020 Jun 30.